CELL PHYSIOLOGY

Homeostasis – maintenance of nearly constant conditions in the internal environment

Feedback system/loop – cycle of events in which the status of a body condition is monitored, evaluated, changed,
remonitored, reevaluated, and so on.

Components:
● Stimulus – any disruption that changes a controlled condition
● Controlled condition – body condition
● Receptor – body structure that monitors changes in a controlled condition and sends input (in the form of nerve
or chemical signals); afferent pathway
● Control center – sets the range of values within which a controlled condition should be maintained (set point),
evaluates the input it receives from receptors, and generates output commands; efferent pathway
● Effector – produces a response/effect that changes the controlled condition
Types:
● Negative – reverses a change in the controlled condition
● Positive – strengthen/reinforce a change in the controlled condition

Chemical Level
Body Fluids
● Solid-40%
● Liquid-60%; F>M- adipose (boobs)
○ ICF- 40 %
○ ECF- 20 %
○ Interstitial- 15%
○ Plasma- 5% (in blood 60%, 40% formed elements)
*Transcellular fluid- components
ICF and ECF composition
● ECF- Na+, Cl-, glucose, bicarbonate, calcium, O2
● ICF- K+, Mg, organic proteins-. lipids, phosphate, sulfate, CO2
○ membrane is more permeable to K+ > Na+ ions

Organic Compounds
1. Carbohydrates
● Monosaccharides - glucose, fructose (fruit), galactose
● Disaccharides - maltose (beer), sucrose (table), lactose (milk)
○ GLU FRU SU
○ GLU GLU MA
○ GLU GALA LA
● Polysaccharides - glycogen (animals), starch (plants) *cellulose - cell walls (not digested)
2. Proteins
● Amino acids - *dipeptide, *tripeptide
● Structural organization
○ 1° - amino acid sequence
○ 2° - alpha helix/beta pleated sheets
○ 3°- 3D
○ 4° - combination of polypeptide chains
3. Lipids
● Fatty acid
○ saturated (all carbons saturated by hydrogen)
○ unsaturated (monounsaturated,polyunsaturated)- healthier
■ d/t presence of covalent bonds
■ Mono - 1 covalent bonds
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 ● Phospholipids -membranous structure phosphate head, 2 fatty acid tail
● Triglyceride - glycerol + 3 fatty acids
○ all fats, proteins, carbs are stored by the liver as triglyceride
○ stored form of energy
● Steroids
○ cholesterol
○ bile salts- fat emulsification
○ hormones (corticosteroids, sex hormones)
● Lipoprotein - *HighDL *LDL
● Vitamins - ADEK (lipid soluble)
● Eicosanoids - Prostaglandins, Leukotrines
○ immunity of chemical messengers

4. Nucleic acid- repeating nucleotides

● DNA - phosphate group, pentose sugar (deoxyribose), nitrogenous bases (A, C, G, T)- 10 pairs
○ *nucleotide- basic component of DNA (phosphate group, sugar, N base)
○ *nucleoside - (-) phosphate group
● RNA - phosphate group, pentose sugar (ribose) nitrogenous bases (A, C, G, U)
> Nitrogenous bases
● Purine- A G (larger, double ring)
● Pyrimidine- C T/U (smaller, single ring)
> Phosphate group (PO43-) or phosphoric acid – alternate with pentose sugars to form the backbone of
the DNA/RNA strand

ATP - energy currency

● Glycolysis - cytoplasm; (-) O2 glucose > 2 ATP + pyruvic acid
○ *pyruvic acid > lactic acid (w/o 02)
○ return to pyruvic acid (need 02); site: liver
■ *myocardium- can use direct lactic acid/direct conversion
○ *pyruvic acid > 2 Acetyl CoA (with 02)
● Krebs/Citric cycle - mitochondria; 2 Acetyl CoA > 2 ATP (with 02)
● Oxidative phosphorylation - mitochondria; hydrogen oxidation (recycling hydrogen) > 34 ATP
● Total: 38 ATP
Eukaryotic vs Prokaryotic
● Eukaryotes have nucleus
Protoplasm – substances that make up the cell, composed mainly of five basic substances:
● Water 70-85%
● Proteins 10-20%
● Lipids-2%
● Carbohydrates-1%
● Ions/Electrolytes

Physical Structure of the Cell

● Cell/Plasma membrane- fluid mosaic model (not rigid); cholesterol is responsible for fluidity; a mosaic of many
different proteins
- Semipermeable/Passes freely: lipids, gases, alcohol (LAG); imperrmeable to glucose*, water urea, and
ions
- Phospholipid
- Proteins- integral (through), peripheral (around)
▪ Channels, carriers, linkers, identity-maker (antigen), enzymes, brush border (microvili)
▪ Glycocalyx- carbohydrate coating (carbohydrates + lipid/proteins)
● glycolipid, glycoproteins
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 ● net (-) charge to repel bacteria
● cell markers
● hydrophilic surface attract a film of fluid to the surface (e.g. makes RBC slippery as
they flow through narrow blood vessels and protects cells that line the airways and the
gastrointestinal tract from drying out)

● Cytoplasm/Cytosol – jelly-like fluid portion of cytoplasm;

○ glycolysis
○ proteasomes (protein degradation)

Organelles

● Endoplasmic reticulum- flat vesicular, lipid bilayer, extending matrix to your nucleus
○ Rough/Granular ER – with ribosomes (protein synthesis)
○ Smooth/Agranular ER – lipid synthesis
o PerOXCisomes –OXidases (form H2O2) , catalase; detOXification, catabolize long chain fatty acids
▪ formed by self-replication or smooth ER

● Ribosomes – composed of RNA & proteins; for protein synthesis

● Golgi Apparatus – thin flat, near nucleus; packaging and processing of substances
○ Lysosomes- lipid bilayer filled hydroLAses; intracellular digestive enzyme
○ Secretory cells/vesicles; forming lysosomes, secretory vesicles and other components

● Mitochondria – powerhouse of the cell, lipid bilayer (outer and inner),

○ inner membrane (cristae) with oxidative enzyme
○ inner cavity is filled with matrix with enzymes for extracting energy from nutrients (produces ATP)
○ self-replicative

● Cytoskeleton – provides rigid physical structures for certain parts of cells

○ Microfilaments – help generate movement and provide mechanical support
i. myofilaments – actin and myosin filaments in muscles fibers
ii. microvilli – nonmotile, fingerlike projections; increases absorption
○ Intermediate filaments – help stabilize the position of organelles and nucleus (flexible scaffolding)
i. vimentin in fibroblasts
ii. cytokeratin in epithelial cells
○ Microtubules – consist of tubulin molecules e.g. flagella and cilia, centrioles and mitotic spindle
i. Cilia – numerous, short, hairlike projections that extend from the surface of the cell; oarlike
pattern
ii. Flagella – longer; wavelike pattern

● Centrosome – consists of two centrioles (short cylinders arranged at right angles), surrounded by pericentriolar
material

● Proteosomes – tiny barrel-shaped structures consisting of four stacked rings of proteins around a central core
○ Proteases-breakdown proteins in the cytoplasm;
Proteasome is a protein complex which degrades unneeded or damaged proteins by proteolysis. Protease is an
enzyme which breaks down proteins and peptides.

● Nucleus – control center of the cell

● Nuclear membrane/envelope – with two lipid bilayer, outer membrane and space are continuous with ER
● Nucleolus – accumulation of large amounts of rRNA subunits
● Nuclear pores
● Nucleoplasm- fluid in nucleus
● Genes – comprised of DNA
● ChromaTIN – in interphase; filamentous at nucleolus
o DNA in histones
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 ● Chromosomes – organized/condensed chromatin material, in mitosis
● Chromatid (kapaTID)- duplicated chromosome; connected by centromere
o Centromere- connection in the middle
o Kinetochore- site of mitotic spindle attachment

Transport of Substances through Cell Membranes

Factors that affect net rate of diffusion

1. Gradient – chemical, electrical, pressure
2. Temperature – the higher, the faster
3. Mass of diffusing substance – the smaller, the faster
4. Surface area – the larger, the faster
5. Diffusion distance – the smaller, the faster

A. PASSIVE Process
a. only its own kinetic energy, across/along the gradient
b. DIFFUSION AND OSMOSIS

I. Diffusion- solute
● Simple diffusion
o Lipid-soluble/hydrophobic/nonpolar substances through the lipid bilayer (LAG)
● O2, CO2, N gases
● Fatty acids, steroids (hormones),and fat-soluble vitamins (A, D, E, and K)
● Alcohol
● Small, uncharged polar molecules (e.g. water, urea, and small alcohols) – though
moderately permeable
● Facilitated diffusion
○ Channel-mediated*: selective permeability; ion-channels*, aquaporins
○ Carrier-mediated – solute binds to a specific carrier; undergoes a change in shape
● Glucose
● *transport maximum/saturation

*The number of carriers available in a plasma membrane places an upper limit, called the transport maximum on the
rate of facilitated diffusion. Saturation occurs when the transport maximum (i.e. all carriers are occupied) is reached,
further increase in concentrated gradient does not increase the rate of facilitated diffusion

*Types of ion channels:

● Leak channels – randomly alternate between open and closed position
● Chemical/ligand-gated – ligand/chemical (e.g. neurotransmitters, hormones, ions) stimulus
● Mechanically-gated – mechanical stimulation (e.g. vibration, touch, pressure, stretch), distorting the channel
from its resting position
● Voltage-gated – change in membrane potential

II. Osmosis – solvent (i.e. water)

● through spaces between phospholipid molecules
● through aquaporins, though hydrated ions cannot pass
● Relate to:
○ hydrostatic (forces movement of water, push; opposite)
○ osmotic pressure (prevents movement of water, pull; same)

Osmolality vs Osmolarity- concern more to number particles instead of mass; the more
osmoles, the higher osmotic pressure
● Osmolality
○ osmoles per kg of water;
● Osmolarity/OsmolaLITER
○ osmoles per liter of solution

Tonicity of solution (i.e. isotonic, hypotonic, hypertonic) *higher to low of solvent/water

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 TONICITY- The ability of an extracellular solution to make water move into or out of a cell by
osmosis is known as its tonicity.

● Hypotonic
○ lysis/rupture (Hi po, pasok ka)
○ solute mas marami INSIDE the cell.
● Hypertonic
○ crenation/shrinkage
○ Solute mas marami sa LABAS ng cell.
B. Active Process
● uses ATP
● against gradient, uphill
● also exhibits transport maximum and saturation
● PRIMARY AND SECONDARY

I. Primary active transport – uses ATP

● Na-K pumps (3NA2Kin)
● Ca pumps
● part of the pump functions as ATPase “PISO”

II. Secondary active transport – indirectly uses energy; uses energy stored in an ionic concentration gradient
established by primary active transport; Carrier: Na
● Co-transport/symport – same direction e.g. Na–glucose and Na–amino acid symporters (foods pasok)
● Counter-transport/antiport – opposite direction e.g. Na–Ca2, Na–H antiporters (NaCaH)

3. Vesicular

1. Endocytosis
a. Receptor-mediated endocytosis – highly selective, cells take up specific ligands.
b. Pinocytosis/bulk-phase endocytosis – ingestion of minute particles/ cell drinking
c. Phagocytosis – ingestion of large particles/ cell eating
2. Exocytosis – releases materials from a cell (e.g. secretory cells, nerve cells), also restoring segments of the
plasma membrane
3. Transcytosis – successively moves a substance into, across, and out of a cell.

Intracellular communication
● Autocrine- self
● Paracrine-neighboring cells
● Endocrine- hormones
● Neural- nerve

Protein Synthesis

Gene Expression
● Transcription- DNA -> mRNA
○ unwinding -> pairing -> preMRNA -> posttranscriptional modification in nucleus (spliceosome) ->
mRNA (template)
○ Intron- spliced part
○ Exons- code for proteins
■ RNA polymerase unwinds DNA helix into two strands
■ Base pairing proceed in a complementary manner
■ Polymerase and the newly formed RNA chain break away from the DNA strand.
■ Resulting transcript is called a pre-mRNA
■ Cutting out the introns and splicing together the exons.
■ The resulting product is a functional mRNA that passes through a nuclear pore to reach the
cytoplasm, where translation takes place.
● Translation- RNA -> protein
■ Initiator tRNA, binds to the start codon (AUG- methionine) on mRNA,
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 ■ tRNA anticodon (UAC) attaches to the mRNA codon (AUG)

START CODON- AUG (August ang start ng class pre pandemic)

STOP CODON- UGA, UAA, and UAG.

RNA – single-stranded
Types of RNA:
● Messenger RNA (mRNA)
■ directs synthesis of protein
■ carries the genetic code to the cytoplasm
● Ribosomal RNA (rRNA)
■ in the nucleolus, where it binds with “ribosomal proteins” to form granular condensation which
form the subunits of ribosomes.
■ Subunits are transported through the nuclear pores to the cytoplasm.
● Transfer RNA (tRNA)
■ binds to an amino acid and holds it in place on a ribosome until it is incorporated into a protein
during translation.
■ One end of the tRNA carries a specific amino acid, and the opposite end consists of a triplet of
nucleotides called anticodon which complements the mRNA codon.

DNA: 3 nucleotides (base triplet)

RNA: 3 nucleotides (codon) which specify a particular amino acid.

Translation:
● Small subunit of a ribosome has a binding site for mRNA
● Larger subunit has three binding sites for tRNA molecules:
○ P (peptidyl) site
○ A (aminoacyl) site (A una sa alphabet)
○ E (exit) site

A site > P site > E site

1. Incoming aminoacy-tRNAs (a tRNA with an amino acid covalently attached is called an aminoacyl-tRNA) enter
the ribosome at the A site.
2. The peptidyl-tRNA carrying the growing polypeptide chain is held in the P site.
3. The E site holds empty tRNAs just before they exit the ribosome

Life Cycle of the Cell

Genes – hereditary units

Genome – total genetic information carried in a cell/organism (46; 22 autosomes pair, 1 sex pair)

● Somatic cells are diploid; each one of the pair of homologues come from each parent.
● Germ cells/gametes are haploid

Interphase – cell is not dividing

Phases:
G1 phase
● High metabolic activity
● Replication of most organelles and cytosolic components.
S (synthesis) phase – DNA replication occurs (Enzyme: DNA Polymerase)
G2 phase
● Cell growth,
G0 phase (Senescence)– cells that remain in G1 for a very long time, perhaps destined never to divide again (e.g.
nerve cells); Telomere shortening
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Mitosis (PMAT) 2 (46)

● Prophase- chromatin -> chromosome -> chromatids, mitotic spindle formation

■ * Prometaphase- (-) nuclear envolope, mitotic spindle attachment to kinetochore
● Metaphase- Midline
● Anaphase- Separation of chromatic
● Telophase- cleavage furrow, (+) nuclear envelope (-) mitotic spindle

*Cytokinesis- replication of cytoplasm

Meiosis 4 (23)
● Prophase I
○ *synapsis - pairing of homolog chromatid to form tetrad > crossing over (homologous recombination) ->
tetrad
● Metaphase I - middle, centrosome of each chromatid; homolog pairs side by side
● Anaphase I - separation of homolog pairs
● Telophase I

● Meiosis II same with Mitosis

Cell Death
Apoptosis- programmed cell death, lysosomes
Necrosis- inflammation, trauma, infection, infarction (type of necrosis; d/t ischemia)

NERVE PHYSIOLOGY
Parts:
● Cell body/soma/perikaryon
● Nissl bodies – rough ER
● Cytoskeleton – neurofibrils (intermediate filaments)
● Lipofuscin – yellowish brown granules, in aging neurons, product of neural lysosomes

● Dendrites – usually short, tapering, and highly branched, propagates signals away from the cell body
● Axon – long, thin, cylindrical projection, propagate signals towards the cell body
● Axon hillock – cone-shaped elevation, joins with the axon
● Initial segment – closest to the axon hillock
● Trigger zone – junction of initial segment and axon hillock, site where action potential arises

● Axoplasm – cytoplasm
● Axolemma – plasma membrane
● Axon collaterals – branches right angle at axon
● Axon terminals/telodendria
○ Synaptic end-bulbs – bulb-shaped structures at the tip
○ Varicosities – string of swollen bumps
○ Synaptic vesicles – stores neurotransmitter ; membrane-enclosed sacs
○ Neurotransmitter – released from a synaptic vesicle that excites or inhibits another neuron, muscle fiber,
or gland cell

● Neurolemma – outer nucleated cytoplasmic layer of the Schwann cell which encloses the myelin sheath
● Nodes of Ranvier – gaps in myelin sheath, fewer in CNS; the axolemma in this region has many voltage-gated
channels compared to regions covered by myelin sheath

Transport Systems:
● Slow axonal transport – conveys axoplasm in one direction only, anterograde “away”

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 ● Fast axonal transport – uses proteins as “motors” to move materials along the surface of microtubules, can be
anterograde (cell body axon terminals; pababa) or retrograde (axon terminals cell body; pataas)
● Orthodromic- typical
○ M: cell body to mm; anterograde
○ S: axon to cell bod; retrograde
● Antidromic- opposite to typical
○ ex: Motor NCV (hallux stimulating-thigh recording) Answer: Retro-Anti
Sensory NCV (fingertip stimulating- FA recording) Answer: Retro- Ortho
Classification:
Structural
Based on number of processes
● Unipolar – dendrites and axon are fused together to form a continuous process that emerges from, the cell body,
trigger zone is located at the junction of the dendrites and axon, cell bodies are located in the ganglia; mostly
sensory
● Bipolar – one dendrite and one axon; found in retina, inner ear, olfactory pathways
● Multipolar – several dendrites and one axon; most neurons are of this type

Based on shape of cells bodies

● Purkinje cells – flask-shaped, in cerebellum
● Pyramidal cells – pyramid-shaped, in cerebral cortex

Resting Membrane Potential – buildup of charge very close to the membrane

● Nerve: -70 mV in neurons (sevenerve)
● Muscle: -90 mV in muscles (siyamuscle)
● Smooth & SA node- -60 mV (smooth sex)

Goldman-Hodgkin-Katz/Goldman equation – diffusion potential depends on three factors:

- polarity of the electrical charge of each ion
- permeability of the membrane to each ion
- concentrations of the respective ions on the inside and outside of the membrane.

Action Potential
● occurs when depolarization reaches a certain level termed the threshold (a rise of 15-30 mV in RMP; exact
point: 55 mV) but does not occur in response to a subthreshold stimulus.
● Follows an all-or-none principle (once generated, the amplitude of an action potential is always the same and
regardless of stimulus intensity)

Stages:
1. Resting – RMP before action potential begins, voltage-gated Na+ (activation gates) and K+ channels are closed;
voltage-gated Na+ channel inactivation gates are open
2. Depolarization – FAST voltage-gated Na+ open, Na+ INFLUX, membrane becomes more POSITIVE inside
3. Repolarization – SLOW voltage-gated K+ open, K+ EFFLUX, membrane becomes more NEGATIVE inside
4. Hyperpolarization- delayed K efflux, more K efflux, MORE NEGATIVE inside

Refractory Period – period of time which an excitable cell cannot generate another action potential in response to a
normal threshold stimulus

● Absolute refractory period – even a very strong stimulus cannot initiate a second action potential;
○ coincides with the period of Na+ channel activation and inactivation
● Relative refractory period – second action potential can be initiated but only by a supramaximal stimulus
○ coincides with the period of K+ channels are still open after inactivated Na+ channels have returned to
their resting state;

Propagation – action potential is not decremental (it does not die out), it keeps its strength as it spreads along the
membrane in all directions away from the stimulus—even along all branches of a nerve fiber—until the entire membrane
has become depolarized.

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 All-or-Nothing Principle – once an action potential has been elicited at any point on the membrane of a normal fiber,
the depolarization process travels over the entire membrane if conditions are right, but it does not travel at all if
conditions are not right

Types:
● Continuous conduction – involves step-by-step depolarization and repolarization of each adjacent segment of
the plasma membrane; occurs in unmyelinated axons and muscle fibers
● Saltatory conduction – action potential appears to “leap” from node to node and travels faster, as the action
potential at the nodes generates ionic currents in the ICF and ECF to depolarize the membrane of succeeding
nodes; since only small regions of the membrane depolarize and repolarize, Na+ inflow and K+ outflow is minimal,
thus less ATP is used by Na+-K+ pump to reestablish the membrane Na+ and K+ gradients to normal; occurs in
myelinated axons

Factors Affecting the Speed of Propagation

- amount of myelination – faster in myelinated axons
- axon diameter – faster in larger diameter axons
- temperature – faster in higher temperature

Graded potential
● small deviation from the RMP, spreads to adjacent regions along the plasma membrane in either direction from
the stimulus source for a short distance and then gradually dies out as the charge are lost across the membrane
through leak channels (decremental conduction)
● Synapses near the soma have far more effect in causing neuron excitation or inhibition than do those that lie far
away from the soma.
● useful for short distance communication only (e.g. postsynaptic potentials, receptor and generator potentials);
modified by summation
● No refractory pd
● In most plasma membrane

Synapse – site of communication between neuron to neuron, or a neuron to an effector cell (e.g. muscle cell or glandular
cell); Connections can be axodendritic (most common), axosomatic or axoaxonic.

Types:
Electrical –
● gap junctions (tunnel to cytosols)
● bi-directional, faster, more synchronized
● occurs in smooth muscles of viscera and cardiac muscles
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 Chemical –
● slower, one way
● presynaptic and postsynaptic neurons are separated by a synaptic cleft
● neurotransmitter

Summation – integration of these postsynaptic potentials

Types:
● Spatial – increasing signal strength by using progressively greater numbers of fibers.
● Temporal –increasing signal strength by increasing the frequency of nerve impulses

Sensory Modalities

● General senses – somatic (e.g. tactile, thermal, pain, proprioceptive), visceral

● Special senses – smell, taste, vision, hearing, balance

Types of Sensory Receptors

Microscopic Structure
● Free nerve endings – bare dendrites (e.g. pain, T°, tickle, itch)
● Encapsulated nerve endings – enclosed in a connective tissue structure (e.g. Meissner, Ruffini, Pacinian
corpuscles)
● Separate cells – special sensory; synapse with 1st order sensory neurons (e.g. hair cells in the inner ear,
gustatory receptor cells in taste buds, photoreceptors of retina- rods and cones)

Receptor Location and Activating Stimuli

● Exteroceptors – monitors external environment
○ Somatoreceptors – monitor stimuli at the body’s surface
○ Teloreceptors – monitor stimuli at a distance from the body (e.g. photoreceptors, olfactory receptors,
auditory)
● Interoceptors/visceroceptors – monitors internal environment
● Proprioceptors – monitors spatial relations of body parts relative to each other (vestibular)

Type of Stimulus Detected

● Mechanoreceptors – mechanical stimuli
● Thermoreceptors – T°
● Nociceptors – pain
● Photoreceptors/electromagnetic receptors – light
● Chemoreceptors – chemical
● Osmoreceptors – osmotic pressure, osmolality (supraoptic nuclei: ADH)
● Baroreceptor- stretch (carotid sinus/aorta)

Nerve Fiber Classification

General
A – myelinated, large, fast NCV, brief refractory period, saltatory conduction, conserve energy
● Aα- extrafusal mm
● Aβ
● Aγ- intrafusal mm
● Aδ
B – small, myelinated; in preganglionic autonomic fibers
C – small, unmyelinated, small, slow NCV, long refractory period: in postganglionic sympathetic fiber

Ia- annulospiral endings

Aα
Ib- GTO

Aβ and Aγ II- flower spray endings discriminative/discrete receptors

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 Aδ III cold temperature, crude touch, fast pain
(pricking, lancinating, superficial, acute,
sharp, electric pain)

C IV hot temperature, crude touch, slow pain

(aching, deep, throbbing, burning,
chronic or nauseous pain)

Somatic Sensations

Tactile
Touch
● Meissner corpuscles – AKA corpuscles of touch; light touch, low-frequency/slow vibration
● Merkel’s discs – AKA Type I cutaneous/tactile discs; continuous touch
○ often grouped together in a receptor organ called the Iggo dome receptor
● Ruffini corpuscles/endings – AKA Type II cutaneous mechanoreceptor; sensitive to stretch
● Pacinian corpuscles – AKA lamellated corpuscle; higher-frequency/fast vibration

Joints:
● I- Ruffini
● II- Pacininan
● III- Golgi Mazzoni
● IV- free nerve

Pressure – Meissner corpuscles, Merkel discs, Pacinian corpuscles

Itch and tickle – free nerve endings, type C
Found in skin and mucous membranes

Thermal – There are more cold spots than hot spots in most areas of the body.
● Cold receptors – Krause-end bulb; within 10-40 °C; type Aδ (with few type C)
● Warm receptors –-Ruffini;; within 32-48°C; type C

Pain
● Nociceptors – free nerve endings; intense thermal (>45 °C), mechanical, or chemical stimuli; found in every body
tissue except brain

Proprioception (also kinesthesia, barognosis, sense of equilibrium)

- Muscle spindle
- Golgi tendon organ
- Joint kinesthetic receptors – free nerve endings, Ruffini corpuscles, Pacinian corpuscles, GTO
- Hair cells of inner ear – in special senses

Adaptation – generator potential or receptor potential decreases in amplitude or frequency during a maintained, constant
stimulus
● Rapidly adapting receptors – detect change in stimulus strength—the “rate receptors,” “movement receptors,” or
“phasic receptors, with predictive function
● Slowly adapting receptors – detect continuous stimulus strength—the “tonic” receptors
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Muscle Spindle

● Measures muscle length or rate of change of length

● Intrafusal muscle fibers with sensory nerve endings enclosed by a connective tissue capsule; interspersed among
most skeletal muscles (except stapedius and tensor tympani) and aligned parallel to extrafusal muscle fibers;
● The central region of these fibers has few or no actin and myosin filaments, does not contract but functions as
sensory receptor.
● Can be excited by:
- lengthening the whole muscle stretches the midportion of the spindle
- contraction of end portions of intrafusal fibers stretches the midportion of the spindle (even if muscle length
remains constant)

Alpha motor neurons – transmit motor signals though alpha efferent fibers to extrafusal fibers
Gamma motor neurons – transmit motor signals through gamma efferent fibers to intrafusal fibers; spasticity inc tone

Nerve fibers
- Afferent fibers – type Ia, type II
- Efferent fibers – type Aα (for extrafusal fibers), type Aγ (for intrafusal fibers)

Intrafusal fibers
- Nuclear bag –Ia;
- Nuclear cha-iin –Ia, II

Responses
- Static – when receptor portion is stretched slowly, both Ia and II are stimulated, directly in proportion to the degree of
stretching, nuclear chain fibers enhances static response

- Dynamic – when receptor portion is stretched rapidly, Ia is stimulated directly in proportion to the rate of change in
spindle length; nuclear bag fibers enhances dynamic response

Muscle Stretch Reflex – monosynaptic

- Static stretch reflex – causes the degree of muscle contraction to remain reasonably constant, except when the
person wills otherwise

● Receptor- Muscle spindle bag chain

● Afferent (S)- Ia II
● Control center- SC
● Efferent- A alpha (excited)
● Effector- mm (cxn)

- Dynamic stretch reflex - opposes sudden changes in muscle length

Renshaw cells – also found in anterior horn, for lateral inhibition - transmission of inhibitory signals to the adjacent
motor neurons of the stimulated motor neuron to focus or sharpen the signal

Golgi Tendon Organ

● Measures muscle tension or rate of change of tension
● autogenic inhibition
● located at the junction of a tendon and a muscle

Static and dynamic response is similar to stretch reflex, static response is proportional to the degree of muscle tension
and dynamic response on the rate of change in muscle tension

Process:
● Receptor- GTO
● Afferent (S)- Ib
● Control center SC (c inhibitory interneuron)
● Efferent- A alpha (inhibited)
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 ● Effector- mm (relax)

Withdrawal reflexes
- Flexor reflex – any cutaneous sensory stimulus flexor withdrawal
- Nociceptive/pain reflex – pain flexor withdrawal, more stronger and prolonged
- Crossed extensor reflex- Occurs shortly after a stimulus elicits a flexor reflex in one limb, wherein the opposite limb
begins to extend

* Denervation hypersensitivity-high to low feedback system; more sensitive than usual -> overfiring of neuron

MUSCLE PHYSIOLOGY
Skeletal Cardiac Smooth

Striated Non striated

Voluntary Involuntary

Long Cylindrical Branched Spindle shape/Fusiform

Multinucleated (periphery) Central nucleus

lacks anatomic and functional Functionally syncytial

connections between individual (e.g. gap junctions in intercalated
muscle fibers discs – transverse thickenings of
plasma membrane attaching each
fiber end to end)

More mitochondria Tonic cxn

Muscle Functions
● Producing body movements
● Stabilizing body positions
● Storing & moving substances within the body
● Thermogenesis

Properties
● Electrical excitability – ability to respond to stimuli producing action potentials
● Contractility – ability to generate tension, irrespective of length
● Extensibility – ability to stretch within limits without being damaged; smooth muscles are subject to greatest
amount of stretch
● Elasticity - ability to return to its original length and shape

SKELETAL MUSCLE

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 *Myoglobin – iron-containing protein similar to hemoglobin, combines with oxygen and stores it until needed speeds
oxygen transport to the mitochondria, gives the muscle a reddish appearance

* Fast Fibers – Type II

● Have more extensive SR for rapid release of Ca++ions, faster contraction velocity
● Large amounts of glycogen and glycolytic enzymes to generate ATP mainly by glycolysis
● Rapid ATP generation and ATP hydrolysis (by myosin ATPase, CPK)
● IIB to IIA - if more on aerobic bc need energy; no conversion from type II to type I

Parts:
● Epimysium- Muscle bulk
● Perimysium- Fascicle “Pascicle”
● Endomysium- Muscle fiber/ muscle cell
● Each fiber is usually innervated by 1 nerve ending near its middle

● Sarcolemma – plasma membrane

● Myofibrils- contractile organelle- sarcomere

Contractile proteins – myofilaments

● Actin – thin filaments, G-actin —> F-actin, each G actin is attached by one molecule of ADP (active site)
● Myosin (II) – thick filaments
○ 2 heavy chains form a helical tail (light meromyosin) on one end,
○ 2 globular heads (heavy meromyosin) on another end, 4 light chains are on the myosin head (2 for each
head)
○ Cross-bridges is axially displaced from the previous pair by 120°
○ Myosin head has myosin ATPase

Regulatory proteins
Troponin
● I (actin, inhibits the interaction of myosin with actin)
● C (contain binding sites for calcium)
● T (binds with tropomyosin)
Tropomyosin – wrapped around actin covering active sites

Structural proteins
● Dystrophin-sarcoglycan complex – reinforces sarcolemma (condition dec dystrophin -> destruction of mm) &
help transmit tension from sarcomeres to tendons
● Titin
○ Z disc to M line, 3rd most plentiful
○ Accounts for much extensibility and elasticity of myofibrils
○ Maintains the central location of A band
● α-actinin
○ dense material of Z disc, binds actin to titin
● Myotilin – also found at the Z-disk
● Telethonin – titin cap
● Myomesin – forms the M line, binds to titin and each myosin
● Nebulin – wraps around actin, helps to anchor them to Z-disc, regulates length of actin
● Desmin – part of binding Z line to plasma membrane
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Sacrotubular system
T system – T tubules, forms a grid perforated by the individual myofibrils; connected to SR
Sarcoplasmic reticulum – ER, regulating Ca++ storage, release, and reuptake and therefore muscle contraction

Sarcomere – between 2 Z-disc, basic functional units of a myofibril

I band – isotropic, light bands, actin, approximates/narrow at cxn
A band – anisotropic (light does not pass thru), dark bands, myosin length and overlapping actin
H zone – center of A band, myosin, space end of actin; obliterated durin cxn
M line – middle, center of H zone, center of myosin
Z disc – center of I band, traverses the whole muscle fiber, attaching the myofibrils all the way across the muscle fiber

Molecular Mechanism of Muscle Contraction

● Excitation-contraction coupling – mechanism by which the action potential causes the myofibrils of muscle to
contract
● Sliding filament mechanism – actin slides inward/ over on the myosin
● Walk-Along/Ratchet theory of contraction – describes the interaction of the “activated” actin and myosin
cross-bridges

Process:
1. Ca++ combine with troponin C (up to 4), troponin complex supposedly undergoes a conformational change,
tugging tropomyosin; “uncovers” the active sites of the actin.
2. Before contraction begins, the heads of the cross-bridges bind with ATP.
3. Myosin ATPase cleaves the ATP and leaves cleavage products (ADP, phosphate) bound to the myosin head; This
causes cocking up of the myosin head
4. Head attaches to an active site in the actin (cross-bridge formation)
5. Power stroke – tilting of the head, release of the ADP and phosphate ion from head
6. At the site of release of the ADP, a new molecule of ATP binds. This binding of new ATP causes detachment of
the head from the actin.
7. Reorient/“Activation” - Myosin ATPase cleaves the ATP into ADP & phosphate, cocking up the myosin head,
ready for the next myosin crossbridge cycle.

Simpler
1. Acetylcholine (open gates for Na) -> Influx of Na (depolarization)
2. Charge of Muscle becomes positive of SR (Ca2+ Storage)
3. Release of Ca2+
4. Ca2+ go to Actin/Thin Filament particularly in Troponin C
5. Exposure of Myosin Binding Site
6. Head attaches to myosin binding site “Power stroke”
7. Thick Filament will pull on the thin filament “Sliding filament theory” = muscle contraction
8. ***Muscle Relaxation - Head must detach from myosin binding site but in order to detach =need/require ATP
9. Detach myosin head to myosin binding site = ATP

Relaxation
● Ca++ pump pumps Ca++ away from the myofibrils and back to SR, returning to normal resting state of cytosolic
Ca++ concentration, which is too little to elicit further contraction

Actin and Myosin Overlap in Tension Generation

● Tension developed by the activated muscle is zero when sarcomere is lengthened at the point where there is no
actin-myosin overlap
● Greatest tension when there is an optimal zone of actin-myosin overlap (sarcomere length: 2-2.22 μm)
● Tension decreases when the sarcomere is shortened at the point where ends of the two actin filaments begin to

Efficiency of Muscle Contraction

● Is the percentage of energy input that is converted into work instead of heat, usually <25%.
● Maximum efficiency can be realized only when the muscle contracts at a moderate velocity (~30% percent of
maximum).

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If the muscle contracts slowly or without any movement, small amounts of maintenance heat are released during
contraction, even though little or no work is performed, thereby decreasing the conversion efficiency to as little as zero.
Conversely, if contraction is too rapid, large proportions of the energy are used to overcome viscous friction within the
muscle itself, and this too reduces the efficiency of contraction.

Motor Unit— all the muscle fibers Innervated by a single nerve fiber,
● small muscles that react rapidly and whose control must be exact have more nerve fibers for fewer muscle fibers
● large muscles that do not require fine control, such as the soleus muscle, may have several hundred muscle
fibers in a motor unit

Different motor units are driven asynchronously; as a result, contraction alternates among motor units one after the other,
thus providing smooth contraction even at low frequencies of nerve signals.

Size principle – allows the gradations of muscle force to occur in small steps, whereas the steps become progressively
greater when large amounts of force are required

Tetany occurs because enough Ca++ ions are maintained in the muscle sarcoplasm, even between action potentials; full
contractile state is sustained without allowing any relaxation between the action potentials.

Staircase Effect/Treppe
When a muscle begins to contract after a long period of rest, its initial strength of contraction may be as little as one half
its strength and rises progressively after a number of twitches later. Postulated to be caused by accumulating Ca++ ions in
the cytosol released by the SR with each successive muscle action potential and failure of the sarcoplasm to recapture
the ions immediately

SMOOTH MUSCLE

Types:
● Unitary/syncytial/visceral – mass of hundreds to thousands of smooth muscle fibers that contract together as a
single unit
● Multi-unit – discrete, separate smooth muscle fibers, contracts independently of the others and often is
innervated by a single nerve ending; found in ciliary muscle and iris muscles of the eye, piloerector muscles

Comparison with Skeletal Muscles

● Slow attachment and detachment of cross-bridges.
○ Latch mechanism – myosin cross-bridges remain attached to actin for prolonged time (even after the
cytoplasmic Ca2+ concentration falls)
● Low energy requirement to sustain muscle contraction – since one molecule of ATP is required for each cycle,
● Maximum force of contraction is greater – due to prolonged attachment of the myosin cross-bridge to the actin
● Stress-relaxation and reverse-stress relaxation – allow smooth muscles to maintain about the same amount of
pressure inside its lumen despite sudden, large, or sustained changes in volume

Contractile Mechanism
● Dense bodies – same role as Z-disc, actin filaments are attached to.
● Myosin filaments have “sidepolar” cross-bridges arranged so that the bridges on one side hinge in one direction
and those on the other side hinge in the opposite direction
○ allows smooth muscle cells to contract as much as 80% of their length (<30 %, as occurs in skeletal
muscle)
● Most Ca++ ions come from influx from ECF (SR in smooth muscles is only slightly developed)
● Latent period - diffusion time of Ca++ ions before the contraction begins; longer in smooth muscles
● SR lie near the caveolae – analogous to T-tubules
● Calmodulin. Ca++ binds with calmodulin (instead of troponin)
● this calcium-calmodulin complex activates myosin light kinase, myosin light kinase phosphorylates the
regulatory chain on myosin head, phosphorylation of myosin head increases myosin ATPase, myosin crossbridge
cycling occurs; In skeletal muscles, phosphorylation is not necessary for activation of the ATPase.

Relaxation
● When the calcium channels close and the calcium pumps are activated.
● Ca++ pumps in smooth muscles are slower, most Ca++ ions are pumped back to ECF than to SR.
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 ● Myosin phosphatase dephosphorylates the regulatory light chain of myosin head; the time required for
relaxation is determined to a great extent by the amount of active myosin phosphatase in the cell.

Neuromuscular Junction
● Autonomic nerve fibers form diffuse junctions that secrete their transmitter substance into the matrix coating. In
few instances, contact junctions (same width of synaptic cleft as to NMJ of skeletal muscles) cause more rapid
contraction.
● Nerve fibers often innervate only the outer layer, muscle excitation travels to the inner layers by action potential
conduction in the muscle mass or by additional diffusion of the transmitter substance.
● Axon terminal have no typical branching end feet, instead they have multiple varicosities distributed along their
axes.

Membrane Potentials
● RMP: -50 to -60 mV
● Action potentials is generated mainly by influx of Ca++ ions than (leaky than usual) Na+
● Spike potentials – similar to skeletal muscles, stimulated by the action of hormones, neurotransmitters, stretch,
or spontaneous generation (repetitive spike potentials induced by slow waves)
● Action potentials with plateaus – with delayed repolarization due to Ca++ influx, account for prolonged
contraction (uterus, ureter)
● Slow wave potentials – AKA pacemaker waves; some smooth muscle is self-excitatory, spontaneous
generation of action potentials are assoc. with slow wave rhythm, caused by waxing and waning of the pumping
of positive ions (e.g. Na+), or conductances of the ion channels increase and decrease rhythmically.

In multiunit smooth muscles (GIT)

● Junctional potential – local depolarization caused by the neurotransmitter, spreads “electrotonically” over the
entire fiber and is all that is necessary to cause muscle contraction
● Synapse en passant- pass synapse from one mm cell to another mm cell
○ Superficial to deep

Energy system
● Fenn effect – the greater the amount of work performed or contraction by the muscle, the greater the amount of
ATP that is cleaved into ADP + phosphate

Sources of the Energy:

● Phosphocreatine –
○ carries a high-energy phosphate bond
○ Its released energy causes bonding of a new phosphate ion to ADP to reconstitute the ATP.
○ Amount of PC is about 5x as great as the ATP.
● Glycolysis –
○ Rapid enzymatic breakdown of the glycogen to pyruvic acid and lactic acid -> energy that is used to
convert ADP to ATP.
○ 2.5 times faster compared to oxidative metabolism.
○ Can occur even in the absence of oxygen.
○ Can sustain muscle contraction for 1 minute

● Oxidative metabolism – provides >95% of all energy used by the muscles for sustained, long-term contraction.
For extremely long-term maximal muscle activity, greatest proportion of energy comes from fats, but for periods
2-4 hours, as much as one half of the energy can come from stored carbohydrates

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