oe a ra 33° yee Shop Y Khoa QContents Preface vi Acknowledgments vii 1. CELLPHYSIOLOGY 1 1 CellMembranes 1 I Transport Across Cell Membranes 2 I, Osmosis 4 W. Diffusion Potential, Resting Membrane Potential, and Action Potential 7 /. Neuromuscular and Synaptic Transmission 12 l. Skeletal Muscle 16 Smooth Muscle 20 i. Comparison of Skeletal Muscle, Smooth Muscle, and CardiacMuscle 22 ReviewTest 23 2. NEUROPHYSIOLOGY 32 1. Autonomic Nervous System (ANS) 32 I SensorySystems 36 Ill. Motor Systems 48 WV. Higher Functions of the Cerebral Cortex 54 V, Blood-Brain Barrier and Cerebrospinal Fluid (CSF) 55 Vi. Temperature Regulation 56 ReviewTest 58 3. CARDIOVASCULAR PHYSIOLOGY 66 |. Circuitry of the Cardiovascular System 66 Hemodynamics 66 Ml Cardiac Electrophysiology 71 IV. Cardiac Muscle and Cardiac Output 76 V. CardiacCycle 85Noi dung Loi néi du vi L6i cém on vii SINH LY TE BAO 1. Mang té bao 1 II. Van chuyén qua mang té bio 2 MI. Thdm thdu 4 IV. Dién thé khuéch tan, Dign thé mang nghi, va Dién thé hoat déng 7 V. Dan truyén than kinh co va Synapse 12 VL Cobamxuong 16 VIL. Co tron 20 VIIL So sinh co bam xuong, co trong, va Co tim 22 Test én tap 23 2. SINH LY THAN KINH 1. H@ than kinh ty chi (ANS) 32 IL Hé camgiéc 36 ML H@ van dong 48 I. Chtic nang cao hon cia vé nao 54 V. Hang rao mau - nao va dich nao tily (CSF) 55 VI. Digu hoa nhiét 46 56 Test én tap 58 3. SINH LY TIM MACH 1. Mach ciia hé tim mach 66 IL. Huyét dong 66 ML. Dign tam do 71 IV. Co tim va Cung lwong tim 76 V. Chukytim 85 32 66Contents ix VI. Regulation of Arterial Pressure 87 Microcirculation and Lymph 91 Special Circulations 94 IX. Integrative Functions of the Cardiovascular System: Gravity, Exercise, and Hemorrhage 97 Review Test 102 vl RESPIRATORY PHYSIOLOGY 115 1. Lung Volumes and Capacities 115 Mechanics of Breathing 117 Gas Exchange 124 /. Oxygen Transport 126 . CO, Transport 131 Pulmonary Circulation 132 V/QDefects 133 Vill, Control of Breathing 135 IX. Integrated Responses of the Respiratory System 137 Review Test 139 RENAL AND ACID-BASE PHYSIOLOGY 147 |. Body Fluids 147 Renal Clearance, Renal Blood Flow (RBF), and Glomerular Filtration Rate (GFR) 151 Reabsorption and Secretion 155 j. NaCl Regulation 158 |. K*Regulation 163 Renal Regulation of Urea, Phosphate, Calcium, and Magnesium 166 Concentration and Dilution of Urine 167 RenalHormones 172 IX. Acid-Base Balance 172 X. Diuretics 181 XI, Integrative Examples 181 Review Test 184 GASTROINTESTINAL PHYSIOLOGY 194 1. Structure and Innervation of the Gastrointestinal Tract 194 Regulatory Substances in the Gastrointestinal Tract 195 Gastrointestinal Motility 199 /. Gastrointestinal Secretion 204 Digestion and Absorption 214 VI. Liver Physiology 219 Review Test 221Noi dung ix VL Digu hda 4p Ine dong mach 87 VIL Vituan hoan va bach huyét 91 VIII. Tuan hoan chuyén bist 94 IX. Chitc nang ph6i hgp cita hé tim mach: Trong lurc, Hoat dng thé lure, va Xudt huyét 97 Test 6n tap 102 4. SINH LY HO HAP 115 I. Thé tich va dung tich phéi 115 IL Co hoc cia su the 117 IIL Trao déi khf 124 Iv. Van chuyén 02 126 V. Van chuyén CO2 131 VL Tuan hoan phéi 132 VIL. Khiém khuyétV/Q 133 VII. Kiém soat hé hdp 135 IX. Céc dap tng phéi hop ciia hé hd hap 137 Testéntap 139 5. SINH LY THAN VA KIEM TOAN 147 L Dich cothé 147 HL D6 thanh thai 6 thn, Luu lwgng mau thin (RBF), vi t6c d9 loc cau than (GFR) 151 IIL Tai hap thu va Bai tiét 155 I. DituhdaNaCl 158 V. DisuhdaKk. — 163 VI. Sy digu hoa cia than déi v6i Urea, Phosphate, Calcium, va Magnesium 166 VIL. Cé dic va pha loaing nuée tiéu 167 VII. Hormonethan 172 IX. Thang bang toan kiém 172 x. Loinigu 181 XL Cécviduphdihop 181 Testén tap 184 6. SINHLY TIEU HOA 194 1 Céu triic va chi phéi than kinh ciia dudng tiéu héa 194 IL Cac chat diéu hda & dudng tiéu héa 195 TIL Nhu d6ng tiéu héa 199 IV. Bai tiét tiéu hoa 204 V. Tiéu héa va hip thy 214 VI Sinh ly gan 219 Testéntap 221x Contents 7. ENDOCRINE PHYSIOLOGY 227 L au. t, Vv. v. uv. vil vil. K, x Overview of Hormones 227 Cell Mechanisms and Second Messengers 229 Pituitary Gland (Hypophysis) 233 ThyroidGland 238 Adrenal Cortex and Adrenal Medulla 241 Endocrine Pancreas-Glucagon and Insulin 248 Calcium Metabolism (Parathyroid Hormone, Vitamin D, Calcitonin) 251 Sexual Differentiation 255 Male Reproduction 256 Female Reproduction 258 ReviewTest 263 Comprehensive Examination 271 Index 293x Noi dung 7. SINH LY NOI TIET 227 1. Tong quan vé Hormones 227 IL. Co ché té bao va chat truyén tin thér hai 229 IIL. Tuyén yén (Hypophysis) 233 IW. Tuyén gidp 238 V. V6 thuong than va Tiythuong than 241 VL. Tuy n6itiét-Glucagon va Insulin 248 VIL. Chuyén héa Calcium (Hormone can giap, Vitamin D, Calcitonin) 251 VIIL. Biéthéa giéi tinh 255 IX. H@ sinh san nam 256 X. Hé sinh san nr 258 Test On tap 263 Kiém traphéi hop 271 Chimuc 2931. CELL MEMBRANES = are composed primarily of phospholipids and proteins. A. Lipid bilayer 1. Phospholipids have a glycerol backbone, which is the hydrophilic (water soluble) head, and two fatty a which are hydrophobic (water insoluble). The hydrophobic tails face each other and form a bilayer. 2, Lipid-soluble substances (c.g., 0,, CO,, steroid hormones) cross cell membranes because they can dissolve in the hydrophobic lipid bilayer. 3. Water-soluble substances (e.g., Na’, Cl, glucose, H,O) cannot dissolve in the li membrane, but may cross through water-filled channels, or pores, or may be trans- ported by carriers. B. Proteins 1. Integral proteins = are anchored to, and imbedded in, the cell membrane through hydrophobic interactions. = may span the cell membrane. = include ion channels, transport proteins, receptors, and guanosine 5’-iriphosphate (GTP)-binding proteins (G proteins). 2. Peripheral proteins «= are not imbedded in the cell membrane. = are nor covalentiy bound to membrane components. = are loasely attached to the cell membrane by electrostati interactions. C. Intercellular connections 1. Tight junctions (zonula occludens) «= are the attachments between cells (often epithelial cells). = maybe an intercellular pathway for solutes, depending on the size, charge, and charac- teristics of the tight junction. = may be “tight” (impermeable), as in the renal distal tubule, or “leaky” (permeable), as in the renal proximal tubule and gallbladder. junctions 2G = are the attachments between cells that permit intercellular communication. «= for example, permit current flow and electrical coupling between myocardial ccnwong J] ———— |. MANG TE BAO © duge du tao chi yéu tir phospholipid va protein, A. Lop kép lipid 1. Phospholipid cé khung glycerol, wa nuéc (tan trong nuéc) va hai dudi acid béo, ky nuée (khong tan trong nuréc}. Cac dudi ky nuréc mat d6i mit véi nhau va tao thanh Ip kép. 2. Céc chat tan trong lipid (vi du: 02, C02, hormone steroid) di xuyén qua mang té bao vi ching c6 thé tan trong lop kép lipid ky nude. 3. Céc chat tan trong mwéc (vi dy: Na+, Cl, glucose, H20) khéng thé tan trong lipid cia mang nhungcé thé di qua céc kénh ngap nu6e, 16 hodc c6 thé duge van chuyén béi cic chat mang. B. Proteins 1. Protein xuyén mang ‘© duoc neo va cdm vao trong mang té bio thong qua céctuong tac ky mu6c. f= 06 thé xdu kim mang té bao. [c6 thé xéu 1 lan hodcnhiéu lan] = bao gdm cdckénh ion, protein vin chuyén, thy thé va protein lin két guanosine S'- triphosphate (GTP) (protein G). 2. Protein ngoai vi (protein bam mang) khong cam vao bén trong mang té bao. © khdng lign két cng héa tri véri céc thanh phiin ciia mang, ‘© duroc gin Iéng Io vao mang té bao bang cic tuong tactinh C. Lién két gian bao 1. Méi néi chat (dai bit) fe 1A phn gan két gitra cdc té bao (thurdmg la té bao biéu md). f= €6 thé Id con dudng gian bao cho céc chat hoa tan di qua, tiy thudc vao kich thuée, dign tich va dic diém cia méinéi chat © 06 thé “chat” (khéngthdm nuéc), nhw & 6ng luon xa cia th4n, hog “rd ri” (thm nuéc), hw 6 dng lugn gan va tii mgt. 2. Méi néi kkhe © 1a phn gin két gitta cdc t8 bao cho phép giao du gian ba "= vidu, cho phép dong dién chay qua va bat cp dién hoc gira cac té bao co tim.2 BRS Physiology Characteristics of Different Types of Transport Electrochemical Carrier- Metabolic —-Na* Tye Gradient Mediated Energy Gradient Simple diffusion Downhill No No No _ Facilitated ditt Downhill Yes No No = Primary active Uphill Yes Yes = Inhibits (it transport Na‘—K* pump) Cotransport Uphill” Yes Indirect Yes, same Inhibits direction Countertranspot Uphill” Yes Indirect Yes, Inhibits opposite rection “One or mare solutes are wansported uphil,Na*is transported éowntil, Il. TRANSPORT ACROSS CELL MEMBRANES (TABLE 1.1) ‘i A. Simple diffusion 1. Characteristics of simple diffusion «= is the only form of transport that is not carrier mediated. = occurs down an electrochemical gradient (“downhill”). = does not require metabolic energy and therefore is passive 2. Diffusion canbe measured using the following eqi J= flux (flow) (mmol/sec) P= permeability (cm/sec) A= area (cm*) concentration, (mmol/L) q C,= concentration, (mmol/L) 3. Sample calculation for diffusion = The urea concentration of blood is 10 mg/100 mL. The urea concentration of proximal tubular fluid is 20 mg/100 mL. If the permeability to urea is 1 x 10 cm/sec and the sur- face area is 100 cm’, what are the magnitude and direction of the urea flux? sux= (2176 V9 em) 20mE 10m sec 100mL 100mL (22 \ on eme)( 108 see i00mL. -(2E2*oooem (228) =1x10* mg/sec from lumen to blood (high tolow concentration) Note: The minus sign preceding the diffusion equation indicates that the direction of flux, or flow, is from high to low concentration. It can be ignored if the higher concen- tration is called C, and the lower concentration is called C,.2 Sinh ly hoc BRS EEE os ciém cia cac oat hinh van chuyén kde nhau Gradient dign Trung Nang Ue ché bom Nar Kigu the gian chat wong ke mang trao déi Khuéch tan don gid Xudi dng Khong Khéng Khang - khuéch tdn thudn héa Xudi done. 6 khong Khone = Van chuyéa Ngurgc dong (ND) C6 6 - Uc ché (nu bom chi dong Nat-K") nguyen phat ‘Bane chuvén No* C6 ianseo C6. cine chibu Ue ch ‘86% chuyén Nguocdong* C6 Giantigp Co, Uc che Nawoc chidu * M@t hodc nhiéu chat tan duce van chuyén ngurgc dong; Na+ dueot van chuyén xubi dong. Il. VAN CHUYEN XUYEN MANG TE BAO (BANG 1.4) [oe =; A. Khuéch tan don gian (Khuéch tan don thuan) 1, Dac diém cia khuéch tan don gian © lahinh thec van chuyén duy nhat khong qua trung gian chat mang, = xy raxudi theo chiéu gradient dign héa (“sui ding”) khong can nding lwgng trao d6i va do dé la thu ding. 2. D6 khuéch tan 06 thé duoc do bang phwong trinh sau: J=-PA(C1-C2) Trong dé: J =luu lugng (mmol/giay) 1 tham (cm/gidy) lig tich (cm?) C1= ndng do 1 (mmol/L) C2= nding dé 2 (mmol/L) du miu v8 cach tinh 6 khuéch tan Nong 49 urea trong mau 1a 10 mg/100 mL. Nong dd urea trong dich dng lron gin 1a 20 mg/100 mL. Néu d6 thdm thdu ca urea la 1 x 10*-5 cm/gidy va dién tich bé mat la 100 em2, thi d@ 16m va huréng cia ding urea Ia bao nhiéu? Luu lugng = (1.x 10*-5 cm/gay) x (100 cm2) x (20 mg/100 mL - 10 mg/100mL) = (1.x 10%-5 cm/gidy) x (100 cm2) x (0.1 mg/em3) =1x 10*-4 mg/gidy theo huéng tirlong 6ng vao mau (tir ndng a cao dén ndng 4d thép) Cha ¥ rang: Dau trir dig trusc phuong trinh khuéch tén cho biét huéng iia ding chay, hodc ding luu luong, li tir noi cé nBng 46 cao dén noi c6 ndng 46 thdp. C6 thé bé qua néu ndng €9 cao hon durge goi la C1 va nding dQ thap hon duoc goi li C2. (Térc ndng dé C1 > C2). ing chit y rang: 1 mL= 1cm*[EXTTEED «Cell Physiology 3 4, Permeability = is the P in the equation for diffusion. = describes the ease with which a solute diffuses through a membrane. = depends on the characteristics of the solute and the membrane. . Factors that increase permeability: = 7 Oil/water partition coefficient of the solute increases solubility in the lipid of the membrane. = {Radius ) of the solute increases the diffusion coefficient and speed of diffusion. = {Membrane thickness decreases the diffusion distance. b. Small hydrophobic solutes (eg, 0,, CO,) have the highest permeabilities in lipid membranes. . Hydrophilic solutes (eg., Na‘, K*) must cross cell membranes through water-filled channels, or pores, or via transporters. If the solute is an ion (is charged), then its flux will depend on both the concentration difference and the potential difference across the membrane. B. Carrier-mediated transport = inchides facilitated diffusion and primary and secondary active transport. = The characteristics of carrier-mediated transport are 1. Stereospecificity. For example, p-glucose (the natural isomer) is transported by facilitated diffusion, but the 1-isomer is not. Simple diffusion, in contrast, would not distinguish between the two isomers because it does not involve a carrier. 2. Saturation. The transport rate increases as the concentration of the solute increases, until the carriers are saturated. The transport maximum (T,) is analogous to the maximum velocity (V, ,) in enzyme kinetics. 3. Competition. Structurally related solutes compete for transport sites on carrier molecules. For example, galactose is a competitive inhibitor of glucose transport in the small intestine. ©. Facilitated diffusion 1. Characteristics of facilitated diffusion = occurs down an electrochemical gradient (“downhill”), similar to simple diffusion. = does not require metabolic energy and therefore is passive. than simple diffusion. = is carrier mediated and therefore exhibits stereospecificity, saturation, and competition. 2. Example of facilitated diffusion = Glucose transport in muscle and adipose cells is “downhill,” is carrier-mediated, and is inhibited by sugars such as galactose; therefore, it is categorized as facilitated diffusion. Indiabetes mellitus, glucose uptake by muscle and adipose cells is impaired because the carriers for facilitated diffusion of glucose require insulin. D. Primary active transport 1. Characteristics of primary active transport = occurs against an electrochemical gradient (‘uphill’). © requires direct input of metabolic energy in the form of adenosine triphosphate (ATP) and therefore is at © is carrier me ted and therefore exhibits stereospecificity, saturation, and competition. 2. Examples of primary active transport a. Na*, K’-ATPase (or Na‘-K* pump) in cell membranes transports Na* from intracellular to extracellular fluid and K* from extracellular to intracellular fluid; it maintains lowsinh Wt t80 3 tham (tinh tham) © 12 Ptrong phuong trinh khuéch tin. = mé ta sy dé dang ma mét chat tan khuéch tn qua mang. ‘© phy thudc vao dic tinh cia chat tan va mang. a. Cac yéu té lam tang tinh tham: © Tang hé s6 thwong sé dau /mur6c ciia chat tan lam tng kha nding hda tan trong lipid ia man; © Gidm ban kinh (kich c) ciia chat tan lam ting hé 36 khuéch tin va t6e d@ khuéch tin, © Giam 46 day mang lam gidm khodng cach khuch tan, b. Céc chat tan ky nue nhé (vi du: 02, C02) 06 kha nang thém thdu cao nhdt trong mang lipid. . Cac chat tan wa nue (vi du: Na+ , K+) phat di xuyén qua mang té bao thong qua céc kenh. ngap nuéc ho3clé mé hodc théng qua cdc phuong tién van chuyén. Néu chat tan 1a mot ion (tich dién), thi dong chay cia né sé phu thudc vao ca chénh léch ndng ¢6 va chénh lech dién théhai bén mang. B. Van chuyén qua trung gian chat mang © gom Khuéch d& dang [Khuéch tan duge thuan héa] va van chuyén cha dong nguyen phat va thit phat. © dc diém cia van chuyén qua trung gian chat mang la 1, Tinh aac higu lap thé. Vi du, D-glucose (dOng phan ty nhién) dugc van chuyén bang hinh, tire khuéch tén thud héa, nhung dng phan L thi khdng. Ngwocigi, khuéch tin don thuin sé Khdng c6 sy phan biét gira hai dng phan viné khdng lién quan dén chat mang. 2. BO bao hoa. Téc d6 van chuyén tang khi ndng dé chat tan tang, cho dén khi chat mang bi bao ha. Tée dé van chuyén ti da (Tm) twong ty nhu técaé tdi da (Vmax] trong dng hoc enzyme. 3. Su canh tranh. Céc chét tan tung dng vé cau tric thi ching sé canh tranh nhau vao cdc vi tri vin chuyén trén cdc phan tir cht mang. Vi du, galactose la chit tee ché canh tranh vin chuyén glucose & rudt non. C. Khuéch tin d8 ding [Ikhuéch tn duge thudn héa] 1. Dic diém cita khuéch tan thuan héa = xdy ra xu6i theo chiéu gradient dign héa ("xu6i dong”), trong tynhurkhuéch tn don gian = Khéng cin ning long trao déi va do dé né thu déng. © nhanh hon khuéch tin don gin. © quatrung gian chat mang va do d6 thé hié tranh, 2. Vidu vé khuéch tén thudn héa ‘© Qué trinh vin chuyén glucose trong cdc té bao co va mé theo dang “xudi dong’, duroc van chuyén qua trung gian chat mang va bi tre ché bi cdc loai during chang han nh galactose; do 46, né dug phan logi 12 khuéch tan thuan héa. Trong d4i tho dwong su hap thu glucose ciia cdc t8 bao co va ma bi suy gidm do cac chat mang trong Khuéch tén thuan héa 6i v6i glucose can cb insulin, nh dc hiGulap thé, 46 bao hoa va sycanh n chuyén chi dong nguyén phat 1. Dic diém cita van chuyén chit dng nguyén phat © xay ra nguoc chiéu gradient dign héa (“ngugc dong’), © cin cung cap tre tiép nang lrong trao d4i diréi dang adenosine triphosphate (ATP) va do d6 durgc goi la chit déng. © 18 hinh thirc van chuyén qua trung gian chat mang, do vay n6 thé hién tinh dc higu lap thé, d6 bao hda va su canh tranh. 2. Vidu vé van chuyén chi: dong nguyén phat a, Na+, K+ -ATPase (hoc bom Na+ -K+) & mang té bio van chuyén Nas tir dich ndi bao ra4 BRS Physiology = Both Na* and K* are transported against their electrochemical gradients. = Energy is provided from the terminal phosphate bond of ATP. © The usual stoichiometry is 3 Na‘/2 K*. «= Specific inhibitors of Na‘, K*-ATPase are the cardiac glycoside drugs ouabain and digitalis. b, Ca?'-ATPase (or Ca?* pump] in the sarcoplasmic reticulum (SR) or cell membranes trans- ports Ca® against an electrochemical gradient. = Sarcoplasmic and endoplasmic reticulum Ca*-ATPase is called SERCA. ¢. HY, K*-ATPase (or proton pump) in gasiric parietal cells transports H* the stomach against its electrochemical gradient. = Itisinhibited by proton pump inhibitors, such as omeprazole, E. Secondary active transport 1. Characteristics of secondary active transport a. The transport of two or more solutesis coupled. , One of the solutes (usually Na*) is transported “downhill” and provides energy for the “uphill” transport of the ather solutes). ©. Metabolic energy is not provided directly but indirectly from the Na* gradient that is maintained across cell membranes. Thus, inhibition of Na’, K*-ATPase will decrease transport of Na’ out of the cell, decrease the transmembrane Na‘ gradient, and eventu- ally inhibit secondary active transport. d. If the solutes move in the same direction across the cell membrane, it is called cotransport or symport. = Examples are Na*-glucose cotransport in the small intestine and renal early proximal tubule and Na*-K*-2CF cotransport in the renal thick ascending limb. @. If the solutes move in opposite directions across the cell membranes, it is called countertransport, exchange, or antiport. = Examples are Na*-Ca** exchange and Na*-H* exchange. 2. Example of Na‘-glucose cotransport (Figure 1.1) a. The carrier for Na*-glucose cotransport is located in the luminal membrane of intesti- nal mucosal and renal proximal tubule cells. bb, Glucose is transported “uphill”; Na* is transported “downhill.” . Energy is derived from the “downhill” movement of Na*. The inwardly directed Na* gradient is maintained by the Na’-K* pump on the basolateral (blood side) membrane. Poisoning the Na‘-K* pump decreases the transmembrane Na* gradient and conse- quently inhibits Na*-glucose cotransport. 3. Example of Na‘-Ca® countertransport or exchange (Figure 1.2) . Many cell membranes contain a Na‘-Ca** exchanger that transports Ca* “uphill” from. low intracellular [Ca”’] to high extracellular [Ca’]. Ca** and Na* move in opposite direc- tions across the cell membrane. b. The energy is derived from the “downhill” movement of Na’. As with cotransport, the inwardly directed Na* gradient is maintained by the Na‘-K* pump. Poisoning the Na" K* pump therefore inhibits Na*—Ca™* exchange. Il. OSMOSIS A. Osmolarity = isthe concentration of osmotically active particles in a solution.4 Sinh ly hoc BRS = CaNa+ va K+ déu duoc van chuyén ngwoc voi gradient dign héa cita ching. = Nang lvgng duc cung cp tir lién két phosphate ngoai cing cia ATP. © Tylwong théng thong la 3 Nat /2 K+. © Thudc te ché dic higu Na+, K+-ATPase la cécthudc glycoside trg tim chinh 1a ouabain va digitatis. b. Ca2+-ATPase (hay bom Ca?) 6 lui co tong (SR) hoac 6 mang té bao van chuyén Ca2+ nguge voi gradient dign héa. © Ca2+ -ATPase 6 lu6i co trong va luéi ndi chat dugc goi 18 SERCA. ©. Ht, K-ATPase (hay bom proton) & céc té bao thanh da day van chuyén H+ vao trong long da day ngwgc v6i gradient dién héa cua n6. = N6bi tie ché bdi cdc thudc tie ché bom proton, ching han nhu omeprazole. E, Van chuyén chit ding thir phat 1. Dac diém cia van chuyén chit ding thir phat a Viéc van chuyén hat hay nhiéu chat tan theo kiéu ghép cap. b, Mét trong cdc chat tan (thuong la Nat) duge van chuyén “xudi ding” va cung cp nang wong cho van chuyén “nguo dong” céc chat tan khéc. Nang luong trao d6i khdng dugc cung cp truc tiép mala gidn tiép tir gradient Na+ duoc dduy tri hai phia mang té bao. Nhu vay, cdc thuéc tie ché Nat, K+ -ATPase sé lam giam van chuyén Na+ ra khdi t8 bo, gidm gradient Nat xuyén mang va cui cing Ia tre ché van chuyén chi déng thir phat. 4, Néu cac chat tan di chuyén theo cing mét huéng xuyén qua mang té bao, né duge goi la dong chuyén hay symport. © Vidy nhw ding chuyén Na+-glucose 6 rudt non va phiin du ng hon gn ctia than va dng chuyén Na+-K+-2CI- nhanh lén day cia than. @. Néu cc chat tan di chuyén ngugc chigu nhau xuyén qua mang té bio, né durgc goi la adi chuyén, trao déi, hay antiport. © Vidy nhw di chuyén Na+-Ca2+ va adi chuyén Na+-H+. du vé dong chuyén Na+-glucose (Hin 1.1) a. Chat mang trong dng chuyén Na+ ~glucose nim trén mang long Ong cla niém mac rugt va t6 bao 6ng lugn gin. b, Glucose dye van chuyén ‘nguge dong’; Na+ duge van chuy€n “xudl dong”. Nang long 6 duge tir sur chuyén dng “xudi dong” cla Na+ . Gradient Na+ huéng vio trong duroc duy tri béi bom Na+-K+ trén mang day bén (phia mau). Ngo d0c bom Na+-K+ 1am gidm gradient Na+ xuyén mang va do dé tte ché dng chuyén Na+ ~glucose. Vi dy ve a6i chuyén hoc trao ai Na+-Ca2+ (Hinh 1.2) . Nhigu mang té bao chia nhan t6 trao 46i Na+-Ca2+ gitip van chuyén Ca2+ “nguoc dong” tir noi c6 [Ca2+] nOi bao thdp dén noi cé6 [Ca2+] ngoai bao cao. Ca2+ va Na+ di chuyén nguge chibu nhau bing qua hai phia ming t8 bao. b, Nang long ¢6 duge tir chuyén dOng “xu! dong” cla Na+ . Ging nhw dong chuyén, gradient Na+ huréng vio trong duroc duy tri bai bom Na+ -K+. Ngo dc bom Nat ~K+ lam dc ch8 qui trin trao d6i Na+ ~Ca2+. ill, THAM THAU aeerr A. potham thau © Ti ndng 46 cia cdc hat c6 hoat tinh tham thu trong dung dich. © Bi mot thudc tinh chung c6 thé do long dugc bing céch ha diém déng bang,Cell Physiology 5 Lumen Intestinal or Blood proximal tubule eel Nat Nat Nat os Ne a FIGURE 1.1 Na*-glucose cotransport(symport)in Secondary SS intestinal cr proximaltubule epithelial cell acive active = can be calculated using the following equation: Osmolarity =g xC where: Osmolarity = concentration of particles (Osm/L) number of paris Insalition (Osm/mo}) leg. Baa= 1 conceston (eet = Two solutions that have the same calculated osmolarity are isosmotic. If two solutions have different calculated osmolarities, the solution with the higher osmolarity is hyperosmotic and the solution with the lower osmolarity is hyposmot = Sample calculation: What is the osmolarity of a 1 M NaCl solution? Osmolarity = gx 2.0sm/molx1M_ =20sm/L B. Osmosis and osmotic pressure ‘= Osmosis is the flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration, 1. Example of osmosis (Figure 1.3) . Solutions 1 and 2 are separated by a semipermeable membrane. Solution 1 contains a solute that is too large to cross the membrane. Solution 2 is pure water. The presence of the solute in solution 1 produces an osmotic pressure. b. The osmotic pressure difference across the membrane causes water to flow from solu- tion 2 (which has no solute and the lower osmotic pressure) to solution 1 (which has the solute and the higher osmotic pressure). ©. With time, the volume of solution 1 increases and the volume of solution 2 decreases. ‘Secondary active Na Gg? ca? + neSinh ly té bao 5 Lang dng Te bao rugehogeté Miu ‘bo 6ng lien gn Nav Nat Nat “Nat Glucose k Nat . NINH 1.1 Ding chuyén Na+ -glucose Chi dong “thi dong (symport) @tébao bigumo éngivon gin th phat nguyen haerudt hat © c6 thé dugc tinh bing phwongtrinh sau: 6 thim thau=gxC Trong dé: DO tham thdu = ndng d9 cita cc hat (Osm/L) 6 lwwong ciia cc hat trong dung dich (Osm/mol) [vi dy, groci=2; guveose= 1] ing 46 (mol/L) ‘© Hai dung dich o6 cing ning dO thm théu tinh todn goi la 18 dng tham. Néu hai dung dich c6 6 tham thu tinh ton khdc nhau, thi dung dich c6 9 thém thdu cao hon duoc goi la wu thm va dung dich c6 6 thm thau th4p hon goi la nhwgc thm. © Vidu tinh toan: Dé thm thdu aia dung dich NaCl 1 M la bao nhiéw BO tham thdu=gxC 2.0sm/mol x 1M 20sm/L B, ‘Thdu théu va 4p sudt thm thau © Tham thau la dong nwée chay xuyén qua mang ban tham tir ch6 dung dich cé ndng d9 chat tan thap sang dung dich c6 ndng dé chattan cao. 1, Vidu v8 thm tha (Hinh 1.3) a, Dung dich 1 va 2 due ngin céch béi mang bin tham. Dung dich 1 chita chat tan qué lén khéng thé vot qua mang. Dung dich 2 la nuéc tinh khiét. Su c6 mat cia chat tan trong dung dich 1 gay ra 4p suat tham thau, b, Su chénh léch v8 4p suit thdm thdu hai bén mang lam cho muéc chiy tir dung dich 2 (kh5ng cé chat tan va 4p sudt thm thdu thdp hon) sang dung dich 1 (c6 chat tan va dp sudt thdm thdu cao hon). ¢. Theo thas gian, thé tich dung dich 1 ting va thé tich dung dich 2 giim. chi atm ee nat pene cae chi ding INH 12 B6ichuyén (antiport) Na-Ca* nguyén phatBRS Physiology we membrane Time . Waier flows oo by osmosis 2o0 from 2-=1 99 90 ooo 1 2 2 FIGURE 1.3 Osmosis of H,O across a semipermeable membrane, 2. Calculating osmotic pressure (van't Hoff's law) a. The osmotic pressure of solution 1 (see Figure 1.3) can be calculated by van't Hoft’s law, which states that osmotic pressure depends on the concentration of osmotically active particles. The concentration of particles is converted to pressure according to the fol- m=gxCxRT where: x= osmotic pressure (mm Hg or atm) ‘= number of particles in solution (osm/mol) C= concentration (mol/L) R= gas constant (0.082 L—atn/mol—K) T= absolute temperature (K) b. The osmotic pressure increases when the solute concentr: increases. A solution of 1M CaCl, has a higher osmotic pressure than a solution of 1 M KC! because the con- centration of particles is higher. ©. The higher the osmotic pressure of a solution, the greater the water flow into it. d. Two solutions having the same effective osmotic pressure are isotonic because no water flows across a semipermeable membrane separating them. If two solutions separated by a semipermeable membrane have different effective osmotic pressures, the solu- tion with the higher effective osmotic pressure is hypertonic and the solution with the lower effective osmotic pressure is hypotonic. Water flows from the hypotonic to the hypertonic solution. @. Colloid osmotic pressure, or oncotic pressure, is the osmotic pressure created by pro- teins (eg., plasma proteins). 3. Reflection coefficient (0) = isa number between zero and one that describes the ease with which a solute perme- ates a membrane. a. If the reflec coefficient is one, the solute is impermeable. Therefore, it is retained in the original solution, it creates an osmotic pressure, and it causes water flow. Serum albumin (a large solute) has a reflection coefficient of nearly one. b, If the reflection coefficient is zero, the solute is completely permeable. Therefore, it will not exert any osmotic effect, and it will not cause water flow. Urea (a small solute) usually has a reflection coefficient of close to zero and it is, therefore, an ineffective osmol 4. Calculating effective osmotic pressure = Effective osmotic pressure is the osmotic pressure (calculated by van't Hof’s law) mul- tiplied by the reflection coefficient. = If the reflection coefficient is one. the solute will exert maximal effective asmotic pres-Sinh ly hoc BRS ee The gian - Dang chay ° ‘ha thé ° thu 2-71 ° 9 -|85805 2 INH 4.3 Sw thém thdu eta #20 qua mang ban thm. . Tinh ap suat tham thau (Dinh luat van't Hoff's) a. Ap suat tham thdu cita dung dich 1 (xem Hinh 1.3) c6 thé duce tinh theo dinh luat van't Hoff, dinh ludt nay phat biéu ring 4p suat thdm thdu phu thudc vao ndng d6 cia céc hat 06 hoat tinh thdm thu. Ning 46 cia cdc hat duge chuyén déi thanh 4p suit theo phurong trinh sau: m= gxCxRT trong dé: ‘n= 4p suét thim thdu (mm Hghogc atm) 6 long hat trong dung dich (osm/mol) C= ndng dé (mol/L) R= hing s6 Khi (0082 L—atm/mol—K) T= nhigt do tuy8t d6i (K) b. Ap suat tham thau tang khi ndng dé chat tan tng. Dung dich CaCl2 1M c6 4p sudt thm thu cao hon dung dich KCI 1 M vi ndng 46 hat nhiéu hon. ¢. Ap suit thdm thau ciia dung dich cang cao thi luu lugngnwéc chiy vao dung dich cang lén. 4, Hai dung dich c6 ciing 4p sudt thdm théu hiéu dung goi li dang truong vi khong cé nuée chay qua mang bén tham ngan céch giita ching. Néu hai dung dich bi ngin céch nhau boi mang ban tham c6 4p sudt thém thau hiéu dung khdc nhau thi dung dich cé Ap suat thém théu higu dung cao hon duge goi la wu trong va dung dich cé 4p suit tham thu higu dung thap hon dugc goi 1a nhwgc trwong. Nwéc chay tir dung dich nhugc trong sang dung dich wu truong. e. Ap suat thdm thau keo, hay 4p suat keo, la 4p sust thim thdu duge tao ra béi protein (vi dy protein huyét trong). H@ s6 phan xa (0) «© Lmét s6 tir 0 dén 1 mé td mic dd d& dang ma chat tan thdm qua mang. a. Néu h@ sd phan xq bang 1, thi chat tan khdng thim nuéc. Do 6, n6 duoc gir lai trong dung dich ban du, né tao ra 4p suit thdm thu va gay ra dong nuéc chiy. Albumin huyét thanh (1a chat tan c6 kich c&lén) c6 hé s6 phan xa gin bing 1. b. Néu hé sé phan xa bing 0, thi chit tan thim hoan toan. Do d6, né sé kh6ng gay ra bat ky higu tng thdm théu nao va sé khOng gay ra dong nwéc chay. Urea (mOt chat tan c6 kich cr ‘nh@) throng 66 hé s6 phan xa gan bang 0 va do d6, né la chat tham thau khong hiéu qua. Tinh 4p sudt thdm théu hiru hic Ap sudt thdm thdu hiru higu [a 4p suat tham thdu (duoc tinh theo dinh luat van't Hoff) nhan vv6i h@ s6 phan xa. © Néu h8 s6 phan xa bang 1, thi chat tan sé tao ra 4p suat thm théu hié phan xa bang 0, thi chat tan sé khong gay 4p suat tham thau. qua t6i da. Néu hé sé[EXTTEED «Cell Physiology 7 IV. DIFFUSION POTENTIAL, RESTING vee F AND ACTION POTENTIAL E A. lon channels ‘= are integral proteins that span the membrane and, when open, permit the passage of cer- tain ions. 1. lon channels are selective; they permit the passage of some ions, but not others. Selectivity is based on the size of the channel and the distribution of charges that line it. = For example, a small channel lined with negatively charged groups will be selective for small cations and exclude large solutes and anions. Conversely, a small channel lined with positively charged groups will be selective for small anions and exclude large sol- utes and cations. 2. lon channels may be open or closed. When the channel is open, the fon(s) for which itis selective can flow through. When the channelis closed, ions cannot flow through, 3. The conductance of a channel depends on the probability that the channel is open. The higher the probability that a channel is open, the higher the conductance, or permeabi ity. Opening and closing of channels are controlled by gates. . Voltage-gated channels are opened or closed by changes in membrane potential. = The activation gate of the Na* channel in nerve is opened by depolarization; when open, the nerve membrane is permeable to Na* (e.g., during the upstroke of the nerve action potential). = The inactivation gate of the Na* channel in nerve is closed by depolarization; when closed, the nerve membrane is impermeable to Na* (e.g., during the repolarization phase of the nerve action potential). b, Ligand-gated channels are opened or closed by hormones, second messengers, or neurotransmitters. = For example, the nicotinic receptor for acetyicholine (ACh) at the motor end plate is an ion channel that opens when ACh binds to it. When open, itis permeable to Na* and K°, causing the motor end plate to depolarize. and equilibrium potentials = A diffusion potential is the potential difference generated across a membrane because of a concentration difference of an ion. = A diffusion potential can be generated only if the membrane is permeable to the ion. = The size of the diffusion potential depends on the size of the concentration gradient. = The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively charged. «= Diffusion potentials are created by the diffusion of very fe result in changes in concentration of the diffusing ions. = The equilibrium potential is the potential difference that would exactly balance (oppose) the tendency for diffusion down a concentration difference. At electrochemical eq ibrium, the chemical and electrical driving forces that act on an ion are equal and opposite, and no more net diffusion of the ion occurs. 1. Example of a Na* diffusion potential (Figure 1.4) a. Twosolutions of NaCl are separated bya membrane that is permeable to Na* but not to Cl. The NaC! concentration of solution 1 is higher than that of solution 2. b. Because the membraneis permeable to Na’, Na* will diffuse from solution 1 to solution 2 down its concentration gradient. CI-is impermeable and therefore will not accom- pany Na‘, ions and, therefore, do not ©. As aresult. a diffusion notential will develon and solution | will become negative withsinh Wt t80 7 IV. BIEN THE KHUECH TAN, BIEN THE NGHI CUA MANG, VA SIEM THE HOAT DONG ae A. Cackénhion © 8 céc protein xuyén mang nam trai dai trén mang va khi mé ra, n6 cho phép mot sé ion nhat dinh di qua 1. Cac kénh ion cé6 tinh chon Io¢; chiing cho phép m@t sé ion di qua, nhumg khéng cho phép cae ion khac di qua. Tinh chon loc dua trén kich thudc cia kénh va sy phan b6 dign tich l6t trong 46. ‘© Vi dy, mt kénh ion nhé durge l6t bang cdc nhém tich dign Am s@ chon loc cic cation nhd va loai triv cdc chat tan én va anion, Ngugc lai, mOt kénh ion nhé duroc lét bang cic nhém tich ign duong sé chon loc cic anion nh6 va loai trir cic chat tan Ion va cation. 2. Cac kénh ion 6 thé md hoge dong. Khi kenh mo, cc ion ma né chon Ic c6 thé chay qua. Khi kénh bi déng, cic ion khéng thé chay qua. dan cita mot kénh phy thudc vio xéc suit mékénh. Kae swat mé kénh cang cao thi dan hodc tinh tha cang cao. Viéc mé va déng céc kénh duoc digu khién boi cdc cng. a. Cac kenh c6 c6ng dign 4p duycme hoac dong bot nhtmng thay d6i ve dign thé mang. © C6ng hoat héa cita kénh Na+ 6 day than kinh duoc mé ra bang qué trinh khir cuc: khi mé, mang cia day thin kinh thém Nat (vi du: trong qué trinh di lén cia dién thé hoat dong day than kinh), © C6ng bat hoat cia kénh Na+ 6 day thin kinh bi déng lai do qué trinh kh aye: khi déng Jai, mang cia day than kinh khdng thdm Na+ (vi du: trong pha tai arc cia dién thé hoat dOngday than kinh), b. Cac kénh c6 céng chat gn mé ho’c dng béi hormone, chat truyén tin thir hai hode chat dan truyén thankinh. © Vidu, thu thé nicotinic gin acetyicholine (ACh) & dia tn cita soi than kinh van dong la mt kénh ion mérra khi ACh lign két voi n5. Khim, né c6 thé thm Nat va K+, lam cho dia tan bj cia sgi than kinh van déng bi Khir cwc. B. Sy'khuéch tan va dign thé cin bing © Dign thé khuéch tan la sw chénh léch dign thé durgc tao ra do su chénh Isch nding ion 2 bén mang, ‘© Chi cé thé tao ra dign thé khuéch tn néu mang cho phép ion thm qua. = DO lon cita dign thé khuéch tan phy thudc vao 46 ln cia gradient ndng 46. = Dau cia dign thé khuéch tén phu thudc vao vigc ion khuéch tan mang dién tich duong hay ‘© Dign thé khuéch tén dugc tgo ra béi sur khuéch tén ca rat it ion va do d6, khong f= dn dén syrthay d6i ndng dé ciia cacion khuéch tan, = Bign thé can bing] sr chénh léch dién thé trong thé cin bing tuyét déi (46i nghich) voi xu hung khudch tn xudi dong theo chénh Iéch ning d0. 0 trang thai can bang dién héa, cic Iue day hoa hoc va dign hoc tac dung 1én mot ion 1a ngang bang va d6i nghich voi nhau, va khong xay ra sy khuéch tan rong cia cacion thém nia. 1, Vidu vé dign thé khuéch tan Na+ (Hinh 1.4) a Hai dung dich NaCl duge ngin cach bi mang ngin thm Na+ nhung khdng thim C-. Nong. 9 NaCI trong dung dich 1 cao hon dung dich 2. b. Do mang thim Na nén Na+ sé Knuéch tén tir dung dich 1 sang dung dich 2 xudi theo chiéu gradient ndng d6 ciia n6, Cl- khOng thdm va do 46 sé khdng di ciing vi Nat. ¢. Két qua la, dién thé khuéch tan sé hinh thanh va dung dich 1 s& tré nén 4m hon so véi dung dich 2,BRS Physiology Na*-selective ‘membrane 1 2 Na* cr cr cr FIGURE 1.4 Generation of an Na* diftusion potential across @ Na*-selective membrane. d. Eventually, the potential difference will become large enough to oppose further net diffusion of Na*. The potential difference that exactly counterbalances the diffusion of Na* downits concentration gradient is the Na* equilibrium potential. At electrochemical equilibrium, the chemical and electrical driving forces on Na* are equal and opposite, and theres no net diffusion of Na’. 2. Example of a Cl- diffusion potential (Figure 1.5) a, Two solutions identical to those shown in Figure 1.4 are now separated by a membrane that is permeable to Cl" rather than to Na*. b. Cl will diffuse from solution 1 to solution 2 down its concentration gradient. Na’ is impermeable and therefore will not accompany Cl. c. A diffusion potential will be established such that solution 1 will become positive with respect to solution 2. The potential difference that exactly counterbalances the diffu- sion of Cl down its concentration gradient is the Cr equilibrium potential. At electro- chemical equilibrium, the chemical and electrical driving forces on Cl are equal and opposite, and there is no net diffusion of C 3. Using the Nemst equation to calculate equilibrium potentials a. The Nernst equation is used to calculate the equilibrium potential at a given concentra- tion difference of a permeable ion across a cell membrane. It tells us what potential would exactly balance the tendency for diffusion down the concenwation gradient; in other words, at what potential would the ion be at electrochemical equilibrium? RT, [ci] B=-2.35. logy oF PSG] where: E= equilibrium potential (mV) at arc 2 C,= intracellular concentration (mM) C, = extracellular concentration (mM) Cr-selective 6 membrane 1 2 1 2 Na* Na* I iF S [er “ PerSinh ly hoc BRS Mang chon lee Nat 1 2 1 2 Nat Na* l~* nar TPs Ne cr Cima! co cr HIN 1.4Sw to ip din thé khuéch tin Nas hai bén mang chon loc Nas. 4. Cu6t cling, sw chénh léch dign thé sé tro nén dit In dé chong lal sw khuéch tan rong them nifa aia Na+. Su chénh léch dign thé lam d6i trong chun xac v6i sw khuéch tan cia Nat ‘xudi theo gradient ndng dé ciia né thi goi li dién thé can bang Na+. O trang thai can bang dign héa, luc dy héa hoc va dign hoc tic dung lén Na+ bing nbau va 61 nghich voi nhau, ding thei khéng 06 su khuéch tan rng cia Nat. 2. Vidy vé dign thé khuéch tén Cl- (Hinh 15) a, Hai dung dich ging hét nhu biéu thi trong Hinh 1.4 hign durge ngin céch bai mot mang thm Cl- chur khong thm Nat b, Cl sékhuéch tan tir dung dich 1 sang dung dich 2 xu6i theo chiéu gradient ning 46 cia n6. Na+ Khdng thm va do d6 sé Khong di km v6i Cl-. © Dign thé khuéch tén sé durge thiét 14p sao cho dung dich 1 s@ tré nén duong hon so v6i dung dich 2. Sur khae biét ve dién thé lam d6i trong chun xc voi su khuéch tén cia Cl- saudi theo gradient ning dé cia né goi Bh dign thé cin bing Cl-. (i trang thdi can bing dién ha, céc lwe dy héa hgc va dién hoc téc dung lén Cl- bang nhau va 46i nghich véi nhau, va khong co sy kiuéch tan rong cua Cl 3, Sir dung phwong trinh Nernst dé tinh dign thé nang cn bing a. Phuong trinh Nernst duoc sir dung dé tinh din thé cin bing trong trudmg hop c6 chénh Iéch ndng a6 nhat dinh cia mot ion thm qua mang té bao. N6 cho chting ta biét ign thé nio sB can bing chun xéc voi xu hung khuéch tin xudi theo gradient ndng 6; noi cach ihc, ion sé 6 trang thai cn bang dign héa 6 dign thé nao? Es -2.3(RT/2F)log(10)[Ci/Ce] trong dé: E=dién thé can bang (mV) 2.3(RT/2F) = 6OmV/2.6 37 6 C z= din tich cita ion (+1 d6iv6i Na‘, +2 461 voi Cae, -1 d6i voi Cl) Ci=ndng dé ndi bao (mM) Ce=ndng d9 ngoai bio (mM) Mang chyn lee or 1 2 1 2 Na* Nat en Gr SS. cro FHINH 1.5 Swtao lip din thé khuéeh tin Cl-at bén mang chon loc Cl.[EXTTEED «Cell Physiology 9 b. Sample calculation with the Nernst equation f= Ifthe intracellular [Na*] is 15 mM and the extracellular (Na’] is 150 mM, what is the ‘equilibrium potential for Na‘? E, 60 mV log,,0.1 +60 mV Note: You need not remember which concentration goes in the numerator. Because it is a log function, perform the calculation either way to get the absolute value of 60 mY. Then use an “intuitive approach” to determine the correct sign. (Intuitive approach: The [Na‘] is higher in extracellular fluid than in intracellular fluid, so Na* ions will diffuse from extracellular to intracellular, making the inside of the cell positive [i.e., +60 mV at equilibrium].) . Approximate values for equilibrium potentials in nerve and muscle E, +65mV a +120 mV Ee -5mV E, -85 mV C. Driving force and current flow = The driving force on an ionis the difference between the actual membrane potential (E,) and the ion’s equilibrium potential (calculated with the Nernst equation). = = Current flow occurs if there is a driving force on the ion and the membrane is permeable to the ion. The direction of current flow is in the same direction as the driving force. The magnitude of current flow is determined by the size of the driving force and the perme- ability (or conductance) of the ion. If there Is no driving force on the ion, no current flow can occur. If the membrane is impermeable to the ion, no current flaw can occur. D. Resting membrane potential = Is expressed as the measured potential difference across the cell membrane in millivolts (mv). = is, by convention, expressed as the intracellular potential relative to the extracellular potential. Thus, a resting membrane potential of -70 mV means 70 mV, cell negati 1. The resting membrane potential is established by diffusion potentials that result from con- centration differences of permeant ions. 2. Each permeable ion attempts to drive the membrane potential toward its equilibrium poten- tial. lons with the highest permeabilities, or conductances, will make the greatest contri- butions to the resting membrane potential, and those with the lowest permeabilities will make little or no contribution. 3. For example, the resting membrane potential of nerve is -70 mV, which is close to the cal. culated K* equilibrium potential of -85 mv, but far from the calculated Na* equilibrium potential of +65 mV. At rest, the nerve membrane is far more permeable to K* than to Na*. 4. The Na’-K’ pump contributes only indirectly to the resting membrane potential by main- taining, across the cell membrane, the Na‘ and K* concentration gradients that then produce diffusion potentials. The direct electrogenic contribution of the pump (3 Na* pumped out of the cell for every 2K* pumped into the cell) is small.sinh Wt t80 9 b, Vidy mau vé tinh ton phuong trinh Nernst fs Néu [Nas] ndi bao 13 15 mM vi [Nas] ngoai bao 18 150 mM, thi dim thé cin bing eta Na+ la bao nhiéu? E(Nat) = -60 mV/z..log (10) [Ci/Ce] = -60 mV/(+1) -Iog (10) [15 mM/ 150 ml] -60 mV . log (10) [0.1] +60 mV Luu §: Ban khéng cin nh6 ndng 46 nim & tir sé nao. Vi day 1A ham log nén hay thy hién phép tinh theo mt trong hai cach dé nhén durgc gia tri tuyét d6i fa 60 mV. Sau d6 st dung ‘mot “phurong phap truc quan” dé xéc dinh dau chinh xc. (Céch tiép cn tryc quan: [Na+] trong dich ngoai bao cao hon trong dich ni bao, vi vay céc ion Na+ s@ khuéch tn tir ngoai bbao vao ndi bao, lam cho bén trong té bao duong [tircla, +60 mV 6 trang thai cin bing}) ¢. Cécgidtri gan duing adi voi dign thé can bang trong day than kinh va co Lye day va dong dién f= Lie day tc dng lén mt ion 18 sux chénh Ich gia dign thé mang thyc té (Em) va dién thé can bang cia ion (duoc tinh bang phuong trinh Nernst). © Dong dign xay ra néu ¢6 luc day téc dung lén ion va mang cho ion thm qua. Chiéu cia dong dién cing chiBu v6i lie dy. Dé I6n ciia dong dién dwac xc dinh bai dé Iém cia hue day va 46 thm (hoc 46 dan) cia ion. Néu khong cé luc dy tac dung Ién ion thi khOng thé xay ra dng ign, NSu mang khong tha ion thi khong thé co dong dign chay qua. D, ign thé nghi ciia mang © dugc biéu tht bing sw chénh Iéch dign thé do duge hai ben mang té bao tinh bang milivolt (nV). ‘© theo quy wéc, né duge biéu thi bing dién thé ndi bao so v6i dién thé ngoai bao. Do dé, dién thé nghi cia mang [a -70 mY c6 nghia 170 mv, t€ bao tich dién am. 1. Dign thé mang lic nghi dwg thiét Ip béi dign thé Ikhuéch tén do chénh léch ndng 46 iia céc ion tham. 2. Mbi ion cé tinh tham d&u c6 ging kéo dién thé mang vé phia dién thé can bang ciia n6. Ac ion c6 d9 thm cao nhat hay a9 dn dien cao nhat sé dong gop nhieu nhat vao dien thé nghi cia mang va nhiing ion cé a6 thm thap nhit sé déng gop it hoe khong déng gop. Vidu, dign thénghi ciia mang day than kinh La -70 mY, gin v6i dién thé cin bing K+ tinh toan li -85 mV, nhung khdcxa dién thé can bang Na+ tinh togn la +65 mV. O trang thai nghi, mang cia day thin kinh thm K+ nhiéuhon Na+. 3 4. Bom Na+ -K+ chi déng gép gidn tiép vio dign thé nghictia mang bing cich duy tri gradient ndng 46 Na+ va K+ hai bén mang té bao ma sau 6 tao ra dign thé khuéch tn, Dong gop sinh dién truc tiép cla bom (3 Na+ dvgc bom ra khoi té bao cho mdi 2 K+ doe bom vio té bio) 18 nhs.BRS Physiology E. Action potentials ions a. Depolarization makes the membrane potential less negative (the cell interior becomes less negative) b. Hyperpolarization makes the membrane potential more negative (the cell interior becomes more negative). ¢. Inward current is the flow of positive charge into the cell. Inward current depolarizes the membrane potential. 4. Outward current is the flow of positive charge out of the cell. Outward current hyperpo- larizes the membrane potential @. Action potential is a property of excitable cells (ie., nerve, muscle) that consists ofa rapid depolarization, or upstroke, followed by repolarization of the membrane potential. Action potentials have stereotypical size and shape, are propagating, and. are all-or-none. {. Threshold is the membrane potential at which the action potential is inevitable. At threshold potential, net inward current becomes larger than net outward current. The resulting depolarization becomes self-sustaining and gives rise to the upstroke of the action potential. If net inward current is less than net outward current, no action potential will occur (ie,, all-or-none response). 2. lonic basis of the nerve action potential (Figure 1.6) a. Resting membrane potential = is approximately ~70 mV, cell negative. = is the result of the high resting conductance to K*, which drives the membrane poten- tial toward the K* equilibrium potential. = Atrest, the Na’ channels are closed and Na* conductance is low. b, Upstroke of the action potential (1) Inward current depolarizes the membrane potential to threshold. (2) Depolarization causes rapid opening of the activation gates of the Na* channels, and the Na* conductance of the membrane promply incr (3) The Na* conductance becomes higher than the K* conductance, and the mem- brane potential is driven toward (but does not quite reach) the Na* equilibrium potential of +65 mV. Thus, the rapid depolarization during the upstroke is caused by an inward Na* current. (4) The overshoot is the brief portion at the peak of the action potential when the mem- brane potential is positive. (5) Tetrodotoxin (TTX) and lidocaine block these voltage-sensitive Na* channels and abolish action potentials. ¢. Repolarization ofthe action potential (1) Depolarization also closes the inactivation gates of the Na* channels (but more slowly than it opens the activation gates). Closure of the inactivation gates results in clo- sure of the Na’ channels, and the Na” conductance returns toward zero. (2) Depolarization slowly opens K* channols and increases K* conductance to even higher levels than at rest. Tetraethylammonium (TEA) blocks these voltage-gated K° channels. (3) The combined effect of closing the Na* channels and greater opening of the K* channels makes the K* conductance higher than the Na‘ conductance, and the membrane potential is repolarized. Thus, repolarization is caused by an outward K¢ current. 4, Undershoot (hyperpolarizing afterpotential) = The K* conductance remains higher than at rest for some time after closure of the Na’ channels. During this period, the membrane potential is driven very close to the + annilihriven nntantial10 Sinh ly hoc BRS Dign thé hoat dong 1. Dinh nghia a, Khir eye fam cho dién thé mang am ft hon (phn bén trong té bao tri nén am ft hon). b. Uu phan cue lam cho din thé ming 4m nhiéu hon (phin bén trong té bio tra: nén am nhiguhon). © Dong dign di vao la dong din tich duong di vao bén trong té bao. Dong dién di vao lam chit ewe dign thé mang 4, Dong dién di ra la dong dién tich dong ra khéi té bao, Dong dién di ra lam wu phan ewe dign thé mang. €. Dign thé hoat dng la mot dac tinh ciia cécté bio dé bi kich thich (tite la day than kinh, co) ‘bao gdm qué trink khit cue nhanh, hay pha di Ién, sau 46 la qué trinh tai cue cia dign thé mang, Cac dién thé hoat dng 6 6 lon va cu dang theo khuén mau, c6 tinh lan truyén va hoat dong theo kiéu tata hoac khong. f. Ngudng 3 dién thé mang ma tai d6 dign thé hoat dng chic chén xay ra. 0’ ngudng dign thé, ding dign di vao tré nén lon hon dong dién di ra. Ket qua la sur khir curc bat dau tur duy ‘tri va Lam tng pha lén cia dién thé hoat déng. Néu déng dién rong di vao nhé hon dong dign rong di ra, thi s® khéng cé dign thé hoat déng nao dién ra (nghia la dp tg theo kiéu tét cd hoc khing). . Cor sé ion cia thé hoat, a. Bign thé nghi cia mang © xp xi-70 mV, t8 bao am. = do d6 dan dign cao bic nghi thé can bang Ks. © O trang thai nghi, cdc kénh Na+ déng va d6 din d6i véi Na+ thap. ing & day than kinh (Hinh 1.6) ri K+, khién cho dign thé mang bi kéo vé phia dién Pha lén cita dién thé hoat dong (1) Dong dign di vao Lam khit aye dién thé mang cham ngudng. (2) Qua trinh Kkhir cuc 1am m6 nhanh céng hoat héa cia céc kenh Nat, va dO din doi voi Nat ciia ming nhanh chéng tang lén, (3) D6 din Na+ bat du c2o hon d6 dn K+ va dién thé mang bi kéo v8 dién thé cn bing Na+ [a +65 mV (nhung khong hoan toan dat durgc). Do 6, qua trinh khtr crc nhanh trong suét pha lén la do dng Na+ di vao. (4) Lén qua tim [a phan dién ra chép nhodng & dinh cia dign thé hoat dng khi din thé mang tré nén duong. (5) Tetrodotoxin (TTX) va lidocaine chin céc kénh Na+ nhay cim vi dién thé nay va trigt tiéu dign thé hoat dong. © Téi cyc cia dign thé hoat dong (1) Qua trinh khir cye cing déng céc céng bat hoat ciia cc kénh Nat (nhung cham hon so véi viée mé céc cng kich hoat). Viée déng céc céng bat hoat dn dén viée déng cdc kénh Na+ va dé dan Na+ vé0. (2) Qué trinh Khir cue mé cham cdc kénh K+ va Lam ting 46 dn K+ lén mic thim chi cao hon so v6i trang thai nghi. Tetraethylammonium (TEA) chin cic kénh K+ c5 cng, dign ap nay. (3) Higu tg két hop ctia viée déng cdc kénh Na+ va mé nhi8u hon céc kénh K+ lam cho 46 din K+ cao hon dQ dan Nat va din thé mang durge tai cur Iai. Do dé, qua trinh tai cue lado dong K+ dira, 4, Xudng qué tam (wu phn cure sau dién thé hoat déng) = D6 dan K+ vin cao hon & trang thi nghi trong mét khong thoi gian sau khi déng cic kenh Na+. Trong thoi ky nay, dign thé mang bi kéo vé rat gan ve phfa dién thé can bing Ke.[EXTTEED «Cell Physiology a Absolute Relative refractory refractory period period +65 mv: Na* equilibrium potential ° | ‘Action potential 2 3 2 8 omv. 5 INa* conductance| 3 g S s are Remus -70 mv" = Resting membrane potential 85 mv- ‘k* equilbrium potential 1.0 20 Time —_> (seq) FIGURE 1.6 Nerve action potential ard associated changes in Na* and K* conductance. 3. Refractory periods (see Figure 1.6) . Absolute refractory period «= is the period during which another action potential cannot be elicited, no matter how large the stimulus. = coincides with almost the entire duration of the action potential. = Explanation: Recall that the inactivation gates of the Na* channels are closed when the membrane potential is depolarized. They remain closed until repolarization ‘occurs. No action potential can occur until the inactivation gates open. b. Relative refractory period = begins at the end of the absolute refractory period and continues until the mem- brane potential returns to the resting level. = An action potential can be elicited during this period only if a larger than usual inward current is provided. = Explanation: The K* conductanceis higher than at rest, and the membrane potential is closer to the K* equilibrium potential and, therefore, farther from threshold; more inward current is required to bring the membrane to threshold. c. Accommodation = occurs when the cell membrane is held at a depolarized level such that the threshold potential is passed without firing an action potential. = occurs because depolarization closes inactivation gates on the Na* channels. = is demonstrated in hyperkalemia, in which skeletal muscle membranes are depol- arized by the high serum K* concentration. Although the membrane potential is closer to threshold, action potentials do not occur because inactivation gates on Na* channelsare closed by depolarization, causing muscle weakness. 4, Propagation of action potentials (Figure 1.7) '= occurs by the spread of local currents to adjacent areas of membrane, which are then dannlarizad tn thrachnld and manarata antian nntantialesinh Wt t80 it ‘Tot ky Thotky tro tuyet trotuong 6i 66 +65 mV. | ign thé can bing Na* wo thenoat dog omv4 06 din Na* ign thé hoc 6 din ee -70 mV} ~ Bign thé nghi cia mang -85 mV: Dign thé can bing 10 20 Ts + INH 1.6 Bignthé hogt ddngeda day thin kinh va nang thay dt ién quan dén 49 dln Na+ va. 3, Thoi ky tro’ (xem Hinh 1.6) a, Théi kj tro tuyét d6i © 1a khodng thei gian ma thich lén dén dau. ‘© tring véi gin nhu toan bé thoi gian cia dién thé hoat ding. © Glat thich: Hay mh6 lai rang céc cOng bat hogt cua céc kénh Na+ dong lat khi dién thé mang bi khit cue. Chiing vin déng cho dn khi qua trinh tii cyc din ra. Khéng c6 din thé hoat déng nao c6 thé dién ra cho dén khi cdc cng bit hoat mé Iai. b. Thoi ky tro tong di © bat dau vao cuéi thai ky tro tuyét déi va tip tue cho dén khi dién thé mang trévé mire nghi. © ign thé hoat dOng chi c6 thé xudt hign trong thd ky nay néu duoc cung cap dng dién di vio lén hon binh throng. thé hoat dOng khac khOng thé dugc khdi phat, bat ké kich én thé mang gan v6i din thé cin bing K+ hon va do dé xa nguéng hon; cin nhi8u ding dién di vao hon 46 dua dién thé mang cham nguéng. ¢. Sw diéu tiét © dién ra khi ming té bio dugc gitr & mite Kir cuc sao cho wot qua dién thé nguong ma khong khéi phat dign thé hoat dong. © din ra do qua trinh khtr are déng cdc o6ng bathoat trén céc kénh Nat. © dugc chimg minh trong tinh trang tang kali mau, trong dé mang co bam xwong bi khtr exc do néng 49 K+ trong huyét thanh cao, Mic dui dién thé mang gin véi ngwong, nhung, dign thé hoat déng khéng xay ra do cic céng bat hoat ciia kénh Na+ bi déng lai do qua trinh khir cur, gay ra hién tong yéu co. 4, Su lan truyén cita dign thé hogt dong (Hinh 1.7) © din ra do sy lan truyén ciia dang dign eye bé dén céc ving lin ke ciia mang, sau 46 duge Khircurcdén ngudng va tao ra dign thé hoat dng.2 BRS Physiology FIGURE 1.7 Unmyelinated axon showing spread of depolarization by local current flow. Box shows active zone where action potential had reversed the polarity Node of Ranvier FIGURE 1.8 Myelirated axon. Action potentials can occur at nodes of Ranvier = Conduction velocity is increased by: a. 1 fiber size. Increasing the diameter of a nerve fiber results in decreased internal resis- tance; thus, conduction velocity down the nerve is faster. b, Myelination. Myelin acts as an insulator around nerve axons and increases conduction velocity. Myelinated nerves exhibit saltatory conduction because action potentials can be generated only at the nodes of Ranvier, where there are gaps in the myelin sheath (Figure 1.8). V. NEUROMUSCULAR AND SYNAPTIC. TRANSMISSION arse A. General charact 1. An action potonti terminal. 2. Asa result of the depolarization, Ca* enters the presynaptic terminal, causing r¢ neurotransmitter into the synaptic cleft. 3. Neurotransmitter diffuses across the synaptic cleft and combines with receptors on the postsynaptic cell membrane, causing a change in its permeability to ions and, conse- quently, a change in its membrane potential. 4. Inhibitory neurotransmitters hyperpolarize the postsynaptic membrane: excitatory neuro- transmitters depolarize the postsynaptic membrane. s of chemical synapses in the presynaptic cell causes depolarization of the presynaptic se of B. Neuromuscular junction (Figure 1.9 and Table 1.2) = isthe synapse between axons of motoneurons and skeletal muscle. = The neurotransmitter released from the presynaptic terminal is ACh, and the postsynaptic membrane contains a nicotinic receptor. 1. Synthesis and storage of ACh in the presynaptic terminal ‘= Choline acetyltransferase catalyzes the formation of ACh from acetyl coenzyme A (CoA) and choline in the presynaptic terminal. ‘= ACh is stored in synaptic vesicles with ATP and proteoglycan for later release. 2. Depolarization of the presynaptic terminal and Ca** uptake = Action potentials are conducted down the motoneuron, Depolarization of the presyn-12 Sinh ly hoc BRS IN 1.7 Soi truc khong c6 bao myelin biéu thi sy lan trayén cia qua trinh khircyc bai dng dién ccuc b9. Hop bisu thi vimg hoat dang -no’ dién thé hoat ding da dao cue. « Bao myelin Nat (eo) Ranvier INH 1.8 Si trac e6 bao myelin. Bign thé hoat dng c6 thé xay ra tai cic eo Ranvier. © Van téc dan truyén duc ting lén bing cich: a. Tang kich c& soi. Tang durdng kinh cia soi thin kinh gidp gidm tr khdng bén trong; do 46 van t6c dn truyén xudi theo day than kinh nhanh hon. b, Myelin héa. Myelin hoat dong nhw mot chat cch dién xung quanh sot truc than kinh va lam ting téc 46 dan truyén. CAc day than kinh c6 bao myelin thé hign tinh din truyén iéu nhay céc vi dién thé hoat dong chi cé thé duge tao ra tai céc mitt Ranvier — ch6 c6 cic Khoang hé tai vo myelin (Hinh 1.8). v. DAN TRUVEN OTHANKINH—COVASYNAPSE A. Dac diém chung cita synapse héa hoc 1, Dign thé hoat déng & té bao tién synapse gay ra sur khir cyc cita dau tan tin synapse. 2. Do qué trinh khit cuc, nén Ca2+ di vao dau tn tién synapse, gay giai phong chat din truyén than kinh vao khe synapse. 3. Chat dan truyén thin kinh khuéch tn bang qua khe synapse va két hop véi cdc thu thé trén ‘mang té bao hau synapse, giy ra su thay d6i tinh tham cia né d6i véi céc ion va do dé lam thay déi din thé mang cia né. 4, Céc chat din truyén than kinh tre ché lam tang phan crcmang hau synapse: céc chat din truyén than kinh kich thich lam khtt cwc mang hau synapse. B, Mot n6i than kinh - co (Hinh 1.9 va Bang 1.2) «= 1a synapse gitta soi truc thin kinh van déng vaco bam xwong. © Chatdan truyén thin kinh duroc gidi ph6ng tir dau tn tin synapse la ACh, va mang hau synapse chira thy thé nicotinic. 1. Téng hop va chira ACh & @au tn tién synapse © Choline acetyltransferase xtic ticsy hinh thanh ACh tir acetyl coenzyme A (CoA) va choline & dau tan tién synapse. ACh dieoe chtta trong cc tii synapse kim véi ATP va proteoglycan dé phéng thich sau nay. 2. Khir cue dau tan tién synapse va hdp thu Ca2+ © Dign thé hoat dong chay xu6i theo neuron vin dng. Qué trinh Khir cwc cia dau tan tig synapse sé lim mé ra cdc kénh Ca2+.[EXTTEED «Cell Physiology B AChR Action potential innewe cp, Nat Motaneuron Muscle FIGURE 1.9 Neuromuscular junction, ACh = acetylcholine; ACHR = acetylcholine receptor. = When Ca** permeability increases, Ca® rushes into the presynaptic terminal down its electrochemical gradient. 3. Ca** uptake causes release of ACH into the synaptic cleft ‘= The synaptic vesicles fuse with the plasma membrane and empty their contents into the cleft by exocytosis. 4. Diffusion of ACh to the postsynaptic membrane (muscle end plate) and binding of ACh to nicotinic receptors = The nicotinic ACh receptor is also aNa* and K* ion channel. ‘= Binding of ACh to « subunits of the receptor causes a conformational change that opens the central core of the channel and increases its conductance to Na* and K*. These are examples of ligand-gated chann 5. End plate potential (EPP) inthe postsynaptic membrane ‘= Because the channels opened by ACh conduct both Na* and K* ions, the postsynaptic membrane potential is depolarized to a value halfway between the Na’ and K’ equilib- rium potentials (approximately 0 mV). = The contents of one synaptic vesicle (one quantum) produce a mi potential (MEPP), the smallest possible EPP. = MEPPs summate to produce a full-fledged EPP. The EPI simply a depolarization of the specialized muscle end plate. 6. Dep ont muscle mombrane to threshold = Once the end plate region isdepolarized, local currents cause depolarization and action potentials in the adjacent muscle tissue. Action potentials in the muscle are followed by contraction. ture end plate ‘not an action potential, but ation of a Agents Affecting Neuromuscular Transmission Effect on Neuromuscular Example Action Transmission Botulinus toxin Blocks release of ACh from Total blockade presynaptic terminals Curere Competes with ACh forreceptors Decreases size of EPP; maximal doses ‘on motor end plate produce paralysis of respiratory muscles and death Neostigmine Inhibits acetylcholinesterase Prolongs and enhances action of ACh at muscle end plate Hemicholinium Blocks reuptake of choline into Depletes ACh stores trom presynaptic terminal Dresynaptic terminalSinh ly té bao 123 "bien thehost dongs day acy thn kinh Neuron van dong co HINH 1.9 M6i néi thin kinh - ox. ACh = acetyicholine; ACHR = thu thé acetylcholine © Khi tinh thdm C22¢ ting lén, thi Ca2+ lao vao dau tan tién synapse xudi theo chi8u gradient dign héa ciza n6. Sw hap thu Ca2+ lam giai phéng ACh vao khe synapse © Cc til synapse hop nhét vot mang té bao va a6 chat chita ca chiing vao Khe nhe qué trinh xuat bao. Khuéch tan ACh dén mang hu synapse (ban tn cita co) va gin ACh vao thy thé nicotini ‘Thu thé nicotinic ctia ACh ciing 1a kénh ion Na+ va K+. f= Su gin cia ACh vao cdc tiéu don vi a cia thy thé gay ra sw thay d6i vé hinh dang lam mé 161 trung tam cia kénh va ting d6 dan ciia né d6i voi Na+ va K+. Day 12 nhieng vi du vé cdc kénh c6 céng chat gan. ign thé ban tan (EPP) 6 mang hu synapse © Boi vi cac kénh durge mé boi ACh dan ca ion Nat va K+, nén dign thé mang hu synapse bi Khir cue dén mot gid tri nm gitka didn thé cn bing Na+ va K+ (xp xi 0 mV). © Cc chat chia trong tii synapse (m6t long tt) tgo ra dign thé ban cudi nhé (MEPP), EPP nhé nhat c6 thé. = MEPP céng g6p lai dé tao ra m6t EPP chinh thitc. EPP khong phai la dign thé hoat dong ‘ma chi don gidn fa sy khir cwe chuyén biét cia ban tan ciia co. Khir cwe mang co’lién ké cham nguong ‘© Sau khi ving ban tan duoc khi cyc, thi dong dién cucb6 gay ra qué trinh Khir cur va tao ra. ign thé hoat déng trong m6 co lan cén. Bién thé hoat ddng 6 co dugc theo sau béi sy co co [co co’sau khi c6 dién thé hoat déng]. free) ic téc nhn anh huréng dn dn truyén thin kinh co Anh hudingdén din truyén view Tac dong ‘than kinh co Botulinustoxin Ngan chan giai phong ACh tir "Ngan chan toan phn eu tn tin synapse Curare Canh tranh véi ACh déivei cde Giim 45 lam ciba EPP; liBu tdi Ga gay lit co” thy thé trén ban tan day than he hip va tir vong kinh vin dng. Necstigmine Ue ché acetylcholinesterase Kéo daiva ting cuéng hoat déng cia ACh & bantén cia cor Hemichelinium hn ti hp thu choline va0 Lam kiét kho chia ACh tir dau t8nti8n synap ‘Ach thiét bi dau tan tin synap, ‘acetylcholine; EPP = dién thé ban tan.4 c. BRS Physiology 7. Degradation of Ach = The EPP is transient because ACh is degraded to acetyl CoA and choline by acetylcholin- esterase (AChE) on the muscle end plate. = One-half of the choline is taken back into the presynaptic ending by Na*-choline cotransport and used to synthesize new ACh. = AChE inhibitors (neostigmine) block the degradation of ACh, prolong its action at the muscle end plate, and increase the size of the FPP. = Hemicholinium blocks choline reuptake and depletes the presynaptic endings of ACh stores. 8. Disease—myasthenia gravis = is caused by the presence of antibodies to the ACh receptor. = is characterized by skeletal muscle weakness and fatigability resulting from a reduced number of ACh receptors on the muscle end plate. ‘= The size of the EPP is reduced; therefore, it is more difficult to depolarize the muscle membrane to threshold and to produce action potentials. ‘= Treatment with AChE inhibitors (c.g, neostigmine) prevents the degradation of ACh and prolongs the action of ACh at the muscle end plate, partially compensating for the reduced number of receptors. Synaptic transmission 1. Types of arrangements ‘a. One-to-one synapses (such as those found at the neuromuscular junction) = Anaction potentialin the presynaptic element (the motor nerve) produces anaction potential in the postsynaptic element (the muscle). b, Many-to-one synapses (such as those found on spinal motoneurons) = An action potential in a single presynaptic cell is insufficient to produce an action potential in the postsynaptic cell. Instead, many cells synapse on the postsynaptic cell to depolarize it to threshold. The presynaptic input may be excitatory or inhibitory. 2. Inputto synapses ‘= The postsynaptic cell integrates excitatory and inhibitory inputs. = When the sum of the input brings the membrane potential of the postsynaptic cell to threshold, it fires an action potential. a. Excitatory postsynaptic potentials (EPSPs) = are inputs that depolarize the postsynaptic cell, bringing it closer to threshold and closer to firing an action potential. = are caused by opening of channels that are permeable to Na* and K*, similar to the ACh channels. The membrane potential depolarizes to a value halfway between the equi- librium potentials for Na* and K* (approximately 0 mV). = Excitatory neurotransmitters include ACh, norepinephrine, epinephrine, dopamine, glutamate, and serotonin. tory postsynaptic potentials (IPSPs) = are inputs that hyperpolarize the postsynaptic cell, moving it away from threshold and farther from firing an action potential. = are caused by opening Cl channels. The membrane potential is hyperpolarized toward the CI" equilibrium potential (-90 mV). «= Inhibitory neurotransmitters are y-aminobutyric acid (GABA) and glycine. 3. Summation at synapses 4. Spatial summation occurs when two excitatory inputs arrive at a postsynaptic neuron simultaneously. Together, they produce greater depolarization.14 Sinh ly hoc BRS . Sir thoai ging ciia Ach «EPP chila thodng qua vi ACh bi thoai ging thanh acetyl CoA va choline bai acetyicholinesterase (AChE) trén dia tan cia co. © MOt ira lvgng choline duge dva tri lai dau tan tien synapse bing céch dng chuyén Na+ - choline va dugc sir dung dé tng hop ACh méi. © Chat tre ché AChE (neostigmine) ngain chin sy phn hily ciia ACh, kéo di téc dung cita n6 tai dia tan cua co va tang do lon cua EPP. «= Hemicholinium ngin chin sw tai hap thu choline va lam can kigt cc kho chifa ACh & dau ‘tn tin synapse. 8, Bénh ly nhugc cor . wr hign dign cia khang thé king lai thu thé ACh, © durore dic true bai sur yéu va mai cia cv bém xwong do gidm s6 lwong thy thé ACh trén dia tan cia co. © DO 16m cia EPP gidm; do dé, vige Khir cuc mang co dn nguéng va tao ra dién thé hoat dong s@ khé khan hon. © Diéu tri bing thudc tre ché AChE (vi du, neostigmine) ngin chin sw phan hity alia ACh va kéo dai hoat dng ciia ACh & dia tan cia co, bi tri mét phn cho sé long thy thé giam_ Dan truyén qua synpase 1. Céc kiéu sp xép a. Céc synapse mOt-mét (ching han nhw céc synapse durgc tim thay & méi ndi thin kinh co) ‘© Dign thé hoat déng & phn ti8n synapse (day thin kinh van déng) gay ra dign thé hoat dong 6 phan hau synapse (co). b. Cac synapse nhiéu-mét (chang han nhw céc synapse dug tim thay trén neuron van dong tiy séng) ‘© Dign thé hoat dong trong té bao tin synapse don dc khdng dit 4é tao ra dign thé hoat Ong trong té bao hau synapse. Thay vao dé, nhiéu té bao tién synapse gin vao té bao hu synapse ri tién hanh khit cue té bao nay dén nguéng. Tin higu Gu vao tién synapse €6 thé la kich thich hodcttc ché. . Tin higu dau vao synapses © Té bao hau synapse tich hop cac tin higu dau vao ca v8 kich thch Ian te ché. 1 Khi téng Ivong tin higu dau vao dura dign th mang cia t bao h4u synapse dén nguémg, né sé cham ngdi mt dign thé hoat déng. a, Dign thé kich thich hju synapse (EPSP) f= [a céc tin hieu cau vao lam khir cure té bao hau synapse, dura né dén gan nguong va gin hon nifa dé cham ngdi mot dién thé hoat dong. © Xay ra do mé cdc kénh thém Na¢ va K¢, trong ty nhu kénh ACh. Dién thé mang khtr cure dat dén mot gia tri mdm gitra dign thé can bang cua Na+ va K+ (xap xi 0 mV). © Chat dan truyén thin kinh kich thich gdm ACh, norepinephrine, epinephrine, dopamine, glutamate va serotonin. b, Dign thé irc ché hau synapse (IPSP) © [a céc tin higu dau vao gay wu phan ewe té bao hau synapse, kéo né ra khoi nguéng va xa hon niga khdi vi cham ngdi iedign théhoat dong. & dy ra do mé kénh. mV). © Chit din truyén than kinh tec ché 18 acid n-aminobutyric (GABA) v3 glycine. }. Su cong gop tai cac synapse a. Cong gop ve khong gian xy ra khi hal tin higu du vao kich thich cing liic ln mt neuron hiu synapse. Chiing cing nhau tao ra sw khir cue lén hon. ign thé mang bi wu phn eye v8 phia dign thé can bang Cl- (-90[EXTTEED «Cell Physiology 15 b. Temporal summation occurs when two excitatory inputs arrive at a postsynaptic neu- ron in rapid succession. Because the resulting postsynaptic depolarizations overlap in time, they add in stepwise fashion. . Facilitation, augmentation, and posttetanic potentiation occur after tetanic stimula- tion of the presynaptic neuron. In each of these, depolarization of the postsynaptic neuronis greater than expected because greater than normal amounts of neurotrans- mitter are released, possibly because of the accumulation of Ca** in the presynaptic terminal. = Long-term potenti 4, Neurotransmitters . ACh (see VB) b. Norepinephrine, epinephrine, and dopamine (Figure 1.10) (1) Norepinephrine « isthe primary transmitter released from postganglionic sympathetic neurons. «= is synthesized in the nerve terminal and released into the synapse to bind with «or B receptors on the postsynaptic membrane. = isremoved from the synapse by reuptake or is metabolized in the presynaptic ter- minal by monoamine oxidase (MAQ) and catechol-O-methyltransferase (COMT). ‘The metabolites are: (a) 3,4-Dihydroxymandelic acid (DOMA) (b) Normetanephrine (NMN) (c) 3-Methexy-4-hydroxyphenylglycol (MOPEG) (a) 3-Methoxy-4-hydroxymandelic acid or vanillyimandelic acid (VMA) = In pheochromocytoma, a tumor of the adrenal medulla that secretes catechol- amines, urinary excretion of VMAis increased. (2) Epinephrine = is synthesized from norepinephrine by the action of phenylethanolamine- N-methyltransferase in the adrenal medulla = amethyl group is transferred to norepinephrine from S-adenosylmethionine jon (memory) involves new protein synthesis. Tyrosine | tyrosine hydroxylase L-dopa dopa decarboxylase Dopamine 1 dopamine B-hydroxylase Norepinephrine | revlenartanine-tietntransterase (adrenal medula) Epinephrine FIGURE 1.10 Synthetic pathway for dopamine, norepi- nephrine, and epinephrine.sinh Wt t80 15 b. Cong gop vé thoi gian xay ra khi hai tin hiéu dau vao kich thich lén mOt neuron hau synapse mét cach lién tiép mau chéng. Do din dén qua trinh khit cuc hau synapse chéng chat lén nhau theo thoi gian, nén ching gp vao theo kiéu bacthang. c. Thuan héa, kéo dai va dién thé sau co cing xAy ra sau kich thich co cig cia neuron tin synapse. Trong mdi trudng hop nay, qué trinh khir curc cia neuron hau synapse lon hon mong doi vi long cht dan truyén than kinh duoc giai phéng nhiu hon binh thudng, €6 thé la dosy tich ty Ca2+ 6 dau tan tién synapse. © Bién thé ha dai han (trinhé) lién quan dén qua trinh tong hop protein moi. 4. Chat dan truyén than kink a. ACh (xem VB) b. Norepinephrine, epinephrine, va dopamine (1 (1) Norepinephrine © Lachat dan truyén chinh duoc giai ph6ng ti cAcneuron giao cam sau hach. © dwoc téng hop & dau tin cia day thin kinh va duoc gidi phéng vao synapse dé lién két véi © thu thé alpha hoac B tén mang hau synapse. © dwoc loai bé khéi synapse bing céch tai hip thu hodc duc chuyén héa & dau tan ti’n synapse béi monoamine oxidase (MAO) va catechol-O-methyltransferase (COMT). Cac chat chuyén héa la: (2) 3,4-Dihydroxymandelic acid (DOMA) (b) Normetanephrine (NMN) (©) 3-Methoxy-4-hydroxyphenylglycol (MOPEG) (@) 3-Methoxy-4-hydroxymandelic acid hoac vanillylmandelic acid (VMA) = Trong pheochromocytoma, dé la mét khéiu cia tiiy thong thin tiét catecholamine, su bai xudt VMA qua nuéc tiéu ting lén. (2) Epinephrie © duoc tng hop tir norepinephrine nha tac dung cia phenylethanolamine-N- rmethyltransferase & ty throng than © m6t nhém methyl duoc chuyén dén norepinephrine tir S-adenosylmethionine 1h 1.10) Tyrosine eres t-dopa terres Dopamine | sopamine hydrolase Norepinephrine phenylethanolamine-N-methyltransferase (tay thurong thin) Epinephrine NINH 1.10 Con dung tng hop cia dopanin, norepinephrine v3 epinephrine.VI. SKELETAL MUSCLE BRS Physiology (3) Dopamine «= js prominent in midbrain neurons. «= is released from the hypothalamus and itis called prolactin-inhibiting factor (PIF). «= is metabolized by MAO and COMT. {a) D, receptors activate adenylate cyclase via a G, protein. {b) D, receptors inhibit adenylate cyclase via a G, protein. (c) Parkinson disease involves degeneration of dopaminergic neurons that use the D, receptors. (a) Schizophrenia involves increased levels of D, receptors. its prolactin secretion; in this context, . Serotonin = is present in high concentrations in the brain stem. «= is formed from tryptophan «= is converted to melatonin in the pineal gland. d. Histamine «= is formed from histidine. «= is present in the neurons of the hypothalamus. e. Glutamate «= is the most prevalent excitatory neurotransmitter in the brain. = There are four subtypes of glutamate receptors. = Three subtypes are ionotropic receptors (ligand-gated ion channels) including the NMDA (N-methyl-v-aspartate) receptor. = One subtype is a metabotropic receptor, which is coupled to ion channels via a heterotrimeric G protein. f. GABA, = isani wry neurotransmitter. «= is synthesized from glutamate by glutamate decarboxylase. = has two types of receptors: (1) The GABA, receptor increases Cl- conductance and is the site of action of benzodi- azepines and barbiturates. (2) The GABA, receptor increases K* conductance. 9. Glycine ‘= is an inhibitory neurotransmitter found primarily in the spinal cord and brain stem. = increases Cl conductance. hh. Nitric oxide (NO) «= is a short-acting inhibitory neurotransmitter in the gastrointestinal tract, blood ves- sels, and the central nervous system. = is synthesized in presynaptic nerve terminals, where NO synthase converts arginine to citrulline and NO. = is apermeant gas that diffuses from the presynaptic terminal to its target cell. = also functions in signal transduction of guanylyl cyclase in a variety of tissues, including vascular smooth muscle. port A. Muscle structure and filaments (Figure 1.11) = Each muscle fiber is multinucleate and behaves as a single unit. It contains bundles of16 Sinh ly hoc BRS (3) Dopamine © c6 mhiéu 6 neuron trung nao. © duoc gidi phOng tir ving du6i di va tee ché tiét prolactin; trong b6i cinh nay, né durgc goi la yu t6 tre ché prolactin (PIF). = duoc chuyén héa bdi MAO va COMT. (a) Cac thy thé D1 kich hoat adenylate cyclase thong qua protein Gs. (b) Cac thy thé D2 irc ché adenylate cyclase théng qua protein Gi. (¢) Bénh Parkinson lién quan dén sw thoai héa cua cacneuron dopaminergic sir dung thy thé D2. (@) ‘Tam than phan Het Hen quan dén vigc tang s6 lwong thu thé D2. © Serotonin © hign din vii ning 46 cao than nao, © dugc hinh thanh tirtryptophan. «= bj chuyn thanh melatonin trong tuyén ting. 4. Histamine © dugc hinh thanh tirhistidine «= hign din trong céc neuron cita viang duéi dBi. @. Glutamate = [a chat din truyén thin kinh kich thich phé bién nhat6 nao. "© 6 bén phan type thu thé glutamate. = 3 phan type Ia céc thy thé ionotropic (cic kénh ion 6 céng chat gin) gbm thu thé NMDA (N-metyl-D-aspartate). = 1 phan type la thu thé metabotropic, né bat cp véi cac kénh ion thong qua protein G heterotrimetric. f. GABA © 1 chat dan truyén than kinh tie ché. © dugc tng hop tir glutamate bi glutamate decarboxylase. f= 6 hai type thu thé: (1) Thy thé GABAA lam ting d6 dan Cl vala noi téc dung cia benzodiazepin va barbiturate. (2) Thy thé GABAB lam tang 40 dan K+. 9. Glycine © 1a chat dfn truyén than kinh tie ché duoc tim thay chii yéu 6 tily sng va than ndo. = am tng a6 dan Cl-. fh, Nitric oxide (NO) © 1a chatdan truyén than kinh tre ché tac dung ngin 6 duong teu h6a, mach mau va he than kinh trungitrong, © duge tng hop 6 cdc dau tn day than kinh ti8n synapse -noi ma NO synthase chuyén arginine thanh citrulline va NO. ‘= 18 Khi thdim khuéch tn tir du tn tin synapse én té bio dich cia né. © cing c6 chic nang dan truyén tin higu cia guanylyl cyclase trong nhiGu loai ma, ké cd co” ‘tron mach mau. er VI. CO’ BAM XUONG eer A. Cau trite va cdc soi co: (Hinh 1.11) MGi soi cu d&u c6 nhigu nhan va hoat dOng nu mdt don vi riéng lé. NO chita cacbs tw co, duro bao boc bai SR va bi chia c&t boi cc dng ngang (6ngT).Coll Physiology " A Motoneuron Sarcomere Muscle 1 I band I bend —=— — Thin Thick filament Myofibri Ziline Miine Zine ‘Sarcolemmal membrane Terminal cisternae ‘Sarcoplasmic reticulum FIGURE 1.11 Structure of the sarcomere in skeletal muscle. A: Arrangement of thick and thir filaments. B: Transverse ‘tubules and sarcoplesmic reticulum. = Each myofibril contains interdigitating thick and thin filaments arranged longitudinally in sarcomeres. = Repeating units of sarcomeres account for the unique banding pattern in striated muscle. A sarcomere runs from line to Z line. 1. Thick filaments ‘= are present in the A band in the center of the sarcomere. ‘= contain myosin. |. Myosin has six polypeptide chains, including one pair of heavy chains and two pairs of light chains. b. Each myosin molecule has two “heads” attached to a single “tail.” The myosin heads bind ATP and actin and are involved in cross-bridge formation. 2. Thin filaments ‘= are anchored at the Z lines.Sinh ly té bao 17 A Neuron vin d6ng co barn vitg co bang! / Bagg wir |__ieres pret” | Teco er aaa zine vach zine Bing Bing a Gngngang BE tan Lirbi cortwong INH 1.11 Céu tric eda dan vi te certrong co bam surong, Su sip xép cia cicsot diy vi soiméng. B:Ong nngang valtcer twang 1 Mai to’co’chita céc soi day va sei méng dan xen véinhau duge sip xép doc theo trong sarcomere. © Cc don vi sarcomere lp di lap lai tgo nén md hinh dai bang d6c do trong co van. Mot sarcomere chay tir vach Z dén vach Z. 1. Soi day © 06 mat trong bang A 6 trung tam sarcomere. = chtta myosin, ‘& Myosin c6 su chudi polypeptide, trong dé c6 mot cp chudi ngng va hai cp chudi nhe. b. M3i phén tir myosin e6 hai “dau” gin v6i m6t “dudi”. Cac du myosin lién két voi ATP va, actin va tham gia vao qué trinh hinh thanh cu n6i chéo. 2 Soi ming © duoc neo tai cicvach Z. = c6 mat trong bang I.B. Steps in excitation-contraction cou . Ttub 3. Intrace BRS Physiology ‘= interdigitate with the thick filaments in a portion of the A band. = contain actin, tropomyosin, and troponin. a, Troponin is the regulatory protein that permits cross-bridge formation when it binds ca. b, Troponin is a complexof three globular proteins: = Troponin T (“T” for tropomyosin) attaches the troponin complex to tropomyosin. ” for inhibition) inhibits the interaction of actin and myosin. = Troponin © (“C” for Ca®*) is the Ca®*-binding protein that, when bound to Ca, permits the interaction of actin and myosin. Ss = are an extensive tubular network, open to the extracellular space, that carry the depolarization from the sarcolemmal membrane to the cell interior. © are located at the junctions of A bands and I bands. = contain a voltage-sensitive protein called the dihydropyridine receptor; depolarization causes. conformational change in the dihydropyridine receptor. . SR «= is the internal tubular structure that is the site of Ca®* storage and release for excitation— contraction coupling. = has terminal cisternae that make intimate contact with the T tubules in a triad arrangement. = membrane contains Ca*-ATPase (Ca pump), which transports Ca’ from intracellular fluid into the SR interior, keeping intracellular [Ca’*] low. = contains Ca** bound loosely to calsequestri = contains aCa** release channel called the ryanodine receptor. fal muscle (Figures 1.12 and 1.13) jing in skel 1. Action potentials in the muscle cell membrane initiate depolarization of the T tubules. 2. Depolarization of the T tubules causes conformational change in its dihydropyridine receptor, which opens Ca** release channels (ryanodine receptors) in the nearby SR, caus- ing release of Ca‘ from the SR into the intracellular fluid. [Ca”*] increases. 4. Ca* binds to troponin € on the thin filaments, causing a conformational change in troponin that moves tropomyosin out of the way. The eross-bridge cycle begins (see Figure 1.12): . Atfirst, no ATP is bound to myosin (A) and myosinis tightly attached to actin. In rapidly contracting muscle, this stage is brief. In the absence of ATR, this state is permanent (ice., rigor). b. ATP then binds to myosin (B) producing a conformational change in myosin that causes myosin to be released from actin. ¢. Myosin is displaced toward the plus end of actin. There is hydrolysis of ATP to ADP and inorganic phosphate (P,). ADP remains attached to myosin (C) d. Myosin attaches to a new site on actin, which constitutes the power (force-generating) stroke (D) AD? is then released, returning myosin to its rigor state. @. The cycle repeats as long as Ca® is bound to troponin C. Each cross-bridge cycle “walks” myosin further along the actin filament. . Relaxation occurs when Ca’* is reaccumulated by the SR Ca**-ATPase (SERCA). Intracellular Ca** concentration decreases, Ca** is released from troponin C, and tropomyosin again blocks the myosin-binding site on actin. As longas intracellular Ca* concentration is low, cross-bridge cycling cannot occur. 3. Mechanism of tetanus. A single action potential causes the release ofa standard amount of Ca” from the SRand produces asingle twitch. However, if the muscle is stimulated repeat-18 Sinh ly hoc BRS © xen ké véi soi day trong mét phan cia bang A. © chia actin, tropomyosin, va troponin. a. Troponin |a protein diéu hda cho phép hinh thanh cau néi chéo khi né lién két voi Ca2+. b. Troponin 1a mot phirc hgp ctia ba protein hinh cau: = Troponin T (“I trong tropomyosin) gin phic hyp troponin vio tropomyosin © Troponin | ("I" trong inhibition [ttc ché]) ttc ché su twong tac claactin va myosin. = Troponin ¢ (°C" trong Ca24) la protein lién két v6i Ca2+, va khi lién két vei Ca2+ n6 cho phép tuong técgiita actin vi myosin. OngT ‘© 1amét mang Iwi hinh 6ng réng khap, thong vao khoang ngoai bao, mang qua trinh khir cyc tirmang bao co vao bén trong té bao. © nam 6 ché néicita bang A va bang I. © chira mét loai protein nhay cm véi dién 4p duoc goi la thu thé dihydropyridin; khir cuc gay ra su thay déi vé cdu dang trong thu thé dihydropyridin. sR © acu tric hinh 6ng bén trong, | noi dw trir va giai phong Ca2+ cho cp kich thich - co. © c6bé tan tiép xtic mat thiét vi dng T 6 dang sp xép bé 3. = ming chira Caz -aTPase (bom CaZ+), giip van chuyén Ca2+ tir dich ndi bao vao bén trong SR, gitr cho [Ca2+] ndi bao & mircthdp. © chia Ca2+ lién két long Iéo véi calsequestrin. © chira kénh giai phéng Ca2+ duge goi la thu thé ryanodine. Céc buréc trong cp kich thich - co & co van (Hin 1.12 va 1.13) 1, Dign thé hoat dong i ming t6 bio co bat dau qui trinh Kh cuc céc Gng T. 2. Sw kit cyre cia ng T giy ra sur thay d6i vé hinh dang ciia thu thé dihydropyridin, mé ra cic kénh gidi phéng Ca2+ (thu thé ryanodine) trong SR lin cin d6, gy ra sw gidi phéng Ca2+ tir SR vio dich ndi bao. 3, [Ca2+] ni bao ting 4, Ca2+ lign két v6i troponin C trén cdc soi méng, gay ra surthay déi vé hinh dang cia troponin lehiga tropomyosin di chuyén ra khdi vi tri ban dau. Chu trinh bit chéo bat dau (xem Hinh 1.12) a. Liic dau, khong ¢6 ATP no gin v6i myosin (A) va myosin gén chat v6i actin. Khi coco nhanh thi giai dogn niy ngén. Khi khong c6 ATP, thi trang thai nay 1a vinh vign (tic 18 co cirng tir thi). b, ATP sau dé lién két v6i myosin (B) tao ra sw thay déi v8 cu dang cia myosin kam cho myosin duoc giai phOng khdi actin. Myosin dich chuyén ve phia dau cOng cia actin. C6 sy thy phan ATP thanh ADP va phosphate v6 co (Pi). ADP van gn véi myosin (C) 4. Myosin gén vio mOt vi tri méitrén actin, sinh ra céng (tao lye) (D) ADP sau dé duroc gidi phéng, dua myosin tré lai trang thai cting di cia né. @. Chu tinh lap lai ching nao Ca2+ cn lien két voi troponin C. MOI chu trinh cau ndi cheo diy myosin “di bd" xa hom doc theo soi actin. 5, Sw dudi dign khi Ca2+ duoc tdi tich tu boi SR Ca2+ -ATPase (SERCA). Nong dd Ca2+ ndi bio ¢gidm, Ca2+ duoc gidi phdng khdi troponin C, va tropomyosin lai ngin chan vi trf gin myosin trén actin. Chirng nao ndng 6 Ca2+ ngi bao cdn thap thi khéng thé xy ra chu trinh cau néi chéo. 6. Cor ché co cing Mét dién thé hoat déng don 1é gay ra sur gidi phéng mét lugng Ca2+ tiéu chudn tir SR va tao ra mot con giat don lé. Tuy mhien, néu co dugc kich thich lap di Kap lai, nhiGu Ca2+ urge giai phéng khdi SR va c6 sw gia ting tich ly [Ca2+] trong ndi bao, thi sé kéo dai thoi gian chu trinh c&u néi chéo. Lic dé bap khong dudi (co ctrng).Cell Physiology 9 Myosin c FIGURE 1.12 Crose-bridge eyele. Myosin “walle” toward the plus end of actin to produce ehortening and force generation. ADP = adenosine dighosphate; ATP = adenosine triphosphate; P,= inorganic phosphate. C. Length-tension and force-velocity relationships in muscle = Isometric contractions are measured when length is held constant. Muscle length (preload) is fixed, the muscle is stimulated to contract, and the developed tension is measured. There is no shortening. = Isotonic contractions are measured when load is held constant. The load against which the muscle contracts (afterload) is fixed, the muscle is stimulated to contract, and shortening is measured. 1. Length-tension relationship (Figure 1.14) ‘= measures tension developed during isometric contractions when the muscle is set to fixed lengths (preload). Action potential we intracellular [Ca] Response FIGURE 1.13 Relationship of he action potental, theSinh ly té bao 19 1HINH 1.22 Chu tinh edu néichéo. Myosin “di bé" v8 pha du cng eta actin dé ty0 ra syn ngin vi sinh ra luc. ADP = adenosin diphosphatw; ATP = adenosine triphosphate; bi = phosphate v6 co. C._M@i quan hé gitra 6 dai-sire c”ing va lyre-van tée trong cor © Co dang truéng duoc do khi chiéu dai dwoc git hing dinh. Chiu dai co (tién tai) duoc co dinh, co duge kich thich 46 co lai va sire cng xuat hién duroc do dac. Khong c6 co ngan co. © Co dang trong dugc do Iti tai dug gitr hang dinh. Tai ma co phai co chdng lai (hu tai) due c6 dinh, cy duge kich thich dé co lai va sw nat ngdn cia co durgc do dac. 1. Méi quan hé gitra chiéu dai-strc cang (Hinh 1.14) © do sire cing hinh thanh trong qué trinh co dng trurdng khi co duroc dat trong béi canh 46 dai c6 dinh (tién tai). 47 Pita the hoat dng f {[ca2*] noibao INH 1.13 Méi quan hé cia dign thé hoat déng,20 BRS Physiology Tension # Length at maximum cross-bridge Active overlan Muscle length FIGURE 1.14 Length-tension relaton- ship in skeletal muscle. a. Passive tension is the tension developed by stretching the muscle to different lengths. b, Total tension is the tension developed when the muscle is stimulated to contract at dif- ferent lengths. ¢. Active tensions the difference between total tension and passive tension. = Active tension represents the active force developed from contraction of the muscle. Itcan be explained by the cross-bridge cycle model. «= Active tension is proportional to the number of cross-bridges formed. Tension will be maximum when there is maximum overlap of thick and thin filaments. When the muscle is stretched to greater lengths, the number of cross-bridges is reduced because there is less overlap. When muscle length is decreased, the thin filaments collide and tension is reduced. 2. Force-velocity relationship (Figure 1.15) = measures the velocity of shortening of isotonic contractions when the muscle is chal- lenged with different afterloads (the load against which the muscle must contract). ‘= The velocity of shortening decreases as the afterload increases. VII. SMOOTH MUSCLE = has thick and thin filaments that are not arranged in sarcomeres; therefore, they appear homogeneous rather than striated. A. Types of smooth muscle 1. Multiunit smooth muscle is present in the iris, ciliary muscle of the lens, and vas deferens. = behaves as separate motor units. volocity of shortening20 Sinh ly hoc BRS Sie cing hibu dat tai aiém chu néichéo géi dy tentang 16ida Chiu dai co INH 1.14 M6i quan he chiu da cang 6 co bam xuong a. Sire cingthy b, Sire cing toan phan la strc cng dugc khdi phat khi co durge kich thich co lai cic dé dai khéc hau. 1a sire cing duoc khdi phat bng cach kéo cng co dén céc 46 dai khéc nhau. ©. Sie cing chii dng la su chénh Iéch gitra site cing ton phn va site cing thy dng, 1 Site cing chi dng thé hién luc chi dng khdi phat tir sur co co. Né c6 thé duoc giai thich bing mo hinh chu trinh cau n6i chéo. Sire cding chii dng ty Is véi s6 lwong cu ndi chéohinh thanh. Site cing sé dat duro ‘cue dai khi c6 su g6i dau cure dai cita cic soi day va ming. Khi co duoc kéo dai hon, sé lung cau n6i chéo se gidm di vico it sur gi dau hon. Khi chiu dai cor glam, cdc soi mong don vio nhau va site cing gam. . Mi quan hé lre-vn tc (Hinh 1.15) © do van t6criit ngin ciia co dng trwong khi co chju thi thach véi cdc hau tai khdc nhau (tai trong ma co phai co dé 461 khang lal). «Van téc rit ngan gidm khi hu tai tang. = a jo VIL. CO TRON a eerrr) © c6 cic soi day va méng khong duoc sp xép 06 trat ty trong sarcomeres; do 46, chting xudt hign dng nhit hon la dang van, A.Xactype cotron 1. Cotronnhiéu don vi c6 trong méng mét, co mi cita thily tinh thé va ng dan tinh. © hoat dong nhu ccdon vi van dong riéng biet. Van técrit rein ban div Mousa HINH 1.45 M6i quan lyc-vin t6e trong corbam xrong.[EXTTEED «Cell Physiology a © has little or no electrical coupling between cells. = is densely innervated; contraction is controlled by neural innervation (e.g, autonomic nervous system). 2. Unitary (single-unit) smooth muscle «= is the most common type and is present in the uterus, gastrointestinal tract, ureter, and bladder. = is spontaneously active (exhibits slew waves) and exhibits “pacemaker” activity (see Chapter 6 II! A), which is modulated by hormones and neurotransmitters. = has a high degree of electrical coupling between cells and, therefore, permits coordi- nated contraction of the organ (e.g., bladder). 3. Vascular smooth muscle = has properties of both multiunit and single-unit smooth muscle. B. Steps in excitation-contraction coupling in smooth muscle (Figure 1.16) © The mechanism of excitation-contraction coupling is different from that in skeletal muscle. = There is no troponin; instead, Ca** regulates myosin on the thick filaments. Depolarization | Hormones or neuretransmitiers | ‘Opens voltage-gated Open ligand-gated (Ca®* channels ‘Ca? channels Cat*-induced Ce2* release Hormones or neurotransmitter \ IPs Ca** release from x 4 from SR tice] | Ca2*-calmodulin (CaM) \ +t Myosin-ight-chain kinase | Phosphorylation of myosin light chains | t Myosin ATPase \ Myosin~P + actin | Cross-bridge cycling \Sinhly tébao 241 & 6 it hod khong e6 két cap dign hoc gitka cdc té bao. © duoc phan b6 than kinh day dc; su co duc kiém soat bdi sw phan bé thin kinh (vi du, hé than kinh tyr chii). 2. Cotron don nhat (1 don vi) «© 1A type phé bién nhat va hién dién trong tir cung, dang tiéu héa, nigu quan va bang quang, . © hoat dong ty phat (biéu hign bang s6ng chi Churong6 III A), hoat déng nay duvgc dieu chinh bai céc hormone inh. © 06 mite 49 cao két cap dién gitra cdc té bao va do d6, cho phép co quan co ce phot hyp (vt du nhur bang quang). 3. Cotron mach mau © c6 dic tinh ca ci co tron don vada don vi. phat nhip” (xem chat dan truyén than B, Céc bw6c trong cap kich thich-co co’ é co'tron (Hinh 1.16) = Corché ciia cp kich thich-co co’ khdc v6i co ché 6 co xuong, = Khéng cé troponin; thay vio dé, Ca2+ didu hda myosin trén cdc sgi day. Sukhircue Hormone hoe Hormone hose | chat din truyén TK Chit dn truyn TK Makeénh Ca2+cécéng — M@kénh C2+.05 Ps dién sp cng chét gin Gili phéng Ca2+do Ca2+ Cazegidi trong luol cotuong, hong ty SR A [cat] | az-calmodulin (CoM) { * sayosin-light-chain kinase | Phosphory! héa chu6i nhe myosin | * Myosin ATPase | Myosin~P + actin \ Chu tinh cau ndi \2 BRS Physiology 1. Depolarization of the cell membrane opens voltage-gated Ca”* channels and Ca** flows into the cell down its electrochemical gradient, increasing the intracellular [Ca]. Hormones and neurotransmitters may open ligand-gated Ca® channels in the cell membrane. Ca” entering the cell causes release of more Ca“ from the SR in a process called Ga*-induced Ca* r Hormones and neurotransmitters also directly release Ca® from the SR through inositol 1,4,5-trisphosphate (IP,}-gated Ca channels. 2. Intracellular [Ca™] increases. 3. Ca** binds to calmodulin, The Ca**—calmodulin complex binds to and activates myosin light chain kinase. When activated, myosin light chain kinase phosphorylates myosin and allows it to bind to actin, thus initiating cross- bridge cycling. The amount of tension produced is proportional to the intracellular Ca’* concentration. 4. Adecrease in intracellular [Ca*] produces relaxation. VIII. COMPARISON OF SKELETAL MUSCLE, SMOOTH MUSCLE, AND CARDIAC MUSCLE = Table 1.3 compares the ionic basis for the action potential and mechanism of contraction in skeletal muscle, smooth muscle, and cardiac muscle. = Cardiac muscle is discussed in Chapter 3. Comparison of Skeletal, Smooth, and Cardiac Muscles Feature Skeletal Muscle Smooth Muscle Cardiac Muscle ‘Appearance Striated No striations Striated Upstroke of action Inward Na* Inward Ca? current Inward C22* current (SA potential current node) Inward Na* current (atta, ventricles, Purkinje fibers) Plateau No No No (SA node) Yes latria, ventricles, Purkinje fibers; due to inward Ca® current) Duration of action ~I msee “10 msee 150 msec (SA node, atria) potential 250-300 msec ventricles and Putkinj fibers) Excitation ‘Action potential Action potential opensvoltage- inward Ca* current during contraction = T tubules gated Ca channels.in cell plateau of action potential coupling membrane ce released Cat induced Ca* release ‘romnearby ‘rom SR SR Tica), Hormones and transmitters Tica, open IP,-gated Ca” channels inSR Molecularbasisfor Ce?*troponin € Ca?*-calmodulin t myosin a?*troponin ¢ contraction chain kinase = inositol 1A S-viohosohate: SA = siroatrial: SR = satcoalzemic reticulum,