The document summarizes normal cardiac anatomy and function. It describes the layers of the heart including the pericardium, epicardium, myocardium, and endocardium. It then details the internal structures of the right and left sides of the heart including the atria, ventricles, valves, papillary muscles, and blood flow. Key points are the four heart valves that direct blood flow, the spongy trabeculated structure of the right ventricle, and the thicker muscular left ventricular wall.
The document summarizes normal cardiac anatomy and function. It describes the layers of the heart including the pericardium, epicardium, myocardium, and endocardium. It then details the internal structures of the right and left sides of the heart including the atria, ventricles, valves, papillary muscles, and blood flow. Key points are the four heart valves that direct blood flow, the spongy trabeculated structure of the right ventricle, and the thicker muscular left ventricular wall.
The document summarizes normal cardiac anatomy and function. It describes the layers of the heart including the pericardium, epicardium, myocardium, and endocardium. It then details the internal structures of the right and left sides of the heart including the atria, ventricles, valves, papillary muscles, and blood flow. Key points are the four heart valves that direct blood flow, the spongy trabeculated structure of the right ventricle, and the thicker muscular left ventricular wall.
Cardiac Anatomy and Histology Pericardium Heart and roots of the great vessels are enclosed by fibroserous sac called the pericardium Consists of two layers: stronger outer fibrous layer and inner serous layer Inner serous layer adheres to external wall of heart and is called the visceral pericardium The visceral pericardium refects back on itself and lines the outer fibrous layer, forming the parietal pericardium Space between visceral and parietal layers contains a thin film of pericardial fluid that allows heart to beat in a minimal friction environment Pericardium is attached to the sternum and the mediastinal portions of the right and left pleurae Its many connections to the surrounding structures keep the pericardial sac firmly anchored within the htorax and thereby help to maintain the heart in its normal position. Emanating from the pericardium superiorly are the aorta, the pulmonary artery, and the superior vena cava The inferior vena cava projects through the pericardium inferiorly Surface Anatomy of the Heart Heart is shaped like a cone and has four muscular chambers Right and left ventricles are the main pumping chambers Less muscular right and left atria deliver blood to their respective ventricles Apex Formed by the tip of the left ventricle, points inferiorly, anteriorly, and tot he left Base/Posterior surface of the heart Formed by atria, mainly the left, and lies between the lung hila Anterior surface of the heart is shaped by the right atrium and ventricle. Because the left atrium and ventricle lie more posteriorly, they form only a small strip of this anterior surface The inferior surface of the heart is formed by both ventricles, primarily the left lies along the diaphragm; also referred to as the diaphragmatic surface From an anteroposterior view (i.e. chest radiograph), four borders of the heart are apparent Right border established by right atrium and almost in line with the superior and inferior venae cavae Inferior border is nearly horizontal and is formed mainly by right ventricle, with a slight contribution from left ventricle near the apex Left ventricle and a portion of the left atrium make up the left border of the heart, whereas the superior border is shaped by both atria From this description, two basic rules of normal cardiac anatomy 1) right sided structures lie mostly anterior to their left-sided counterparts 2) Atrial chambers are located mostly to the right of their corresponding ventricles Internal Structure of the Heart Four major valves direct blood flow in a forward direction and prevent backward leakage atrioventricular (AV) valves (tricuspid and mitral) separate the atria and ventricles, whereas the semilunar valves (pulmonic and aortic) separate the ventricles from the great arteries. All four heart valves are attached to fibrous cardiac skeleton, which is composed of dense connective tissue. Cardiac skeleton also serves as a site of attachment for the ventricular and atrial muscles Figure 1.3: The four heart valves viewed from above with atria removed Tricuspid and mitral valves are open and the semilunar valves (pulmonic and aortic) are closed Each annulus fibrosus surrounding the mitral and tricuspid valves is thicker tha those surroundign the pumonic and aortic valves All four contribute to heart fibrous skeleton, which is composed of dense connective tissue. Surface of heart valves and interior surface of the chambers are lined by a single layer of endothelial cells aka endocardium. Subendocardial tissue contains fibroblasts, elastic, and collagenous fibers, veins, nerves, and branches of the conducting system Continuous with the connective tissue of the heart muscle layer, the myocardium. Myocardium is the thickest layer of the heart and has bundles of cardiac muscle cells External to myocardium is a layer of connective tissue and adipose tissue through which pass the larger blood vessels and nerves that supply the heart muscle Epicardium is the outermost layer of the heart and is identical to, and just another term for, visceral pericardium. Right atrium and Ventricles Superior and inferior venae cavae and coronoary sinus open into right atrium Venae cavae return deoxygenated blood from systemic veins into the right atrium, whereas the coronary sinus carries venous return from the coronary arteries. Interatrial septum forms posterormedial wall of right atrium and separates it from th left atrium Tricuspid valve is located in the floor of the atrium and opens into right ventricle Right ventricle is roughly triangular in shape, and its superior aspect form a cone-shaped outflow ract, which leads to the pulmonary artery. Although the inner wall of the outflow tract is smooth, the rest of the ventricle is covered by a number of irregular bridges (trabeculae carneae) that give right ventricular wall a spongelike apperance. A large trabecula that crosses the ventricular cavity is called the moderator band. It carries a component of the right bundle branch of the conducting system to the ventricular muscle. Right ventricle contains three papillary muscles, which project into the chamber and via their thin, stringlike chordae tendineae attach to the edges of the tricuspid valve leaflets. The leaflets are attached to fibrous ring that supports the valve between the right atrium and ventricles Contraction of the ppapillary muscles prior to other regions of the ventricle tightens the chordae tendineae, helping to align and restrain the leaflets of the tricuspid valve as they are forced closed. This prevents blood from regurgitating into right atrium during ventricular contraction. At apex of right ventricular outflow tract is the pulmonic valve, which leads to the pulmonary artery. This valve consists of three cusps attached to a fibrous ring. During relaxation of ventricle, elastic recoil of the pulmonary arteries forces blood back torward the heart, distending the valve cusps toward one another. This action closes the pulmonic valve and prevents regurigation of blood back into right ventricle Left Atrium and Ventricle Four pulmonary veins enter the posterior half of left atrium Wall of left atrium is ~ 2mm thick, slightly greater than that of the right atrium. Mitral valve opens into left ventricle through inferior wall of the left atrium Cavity of left ventricle is approximately cone shaped and longer than right ventricle's. In healthy adult heart, wall thickness is 9 to 11 mm, ~ three times that of the right ventricle. Aortic vestibulte is smooth walled part of left ventricular cavity, located inferior to the aortic valve. Inferior to this region, most of the ventricle is covered by trabeculae carneae, which are finer and more numerous than those in right ventricle. Left ventricular chamber has two large papillary muscles Larger than counterparts in right ventricle; their chordae tendineae thicker but less numerous Chordae tendineae of each papillary muscle distribute to both leaflets of mitral valve. Tensing of chordae tendineae during left ventricular contraciton helps restrain and align the mitral leaflets, enabling them to close properly and preventing backflow. Aortic valve sparates the left ventricle from aorta Surrounding aortic valve opening is fibrous right, which has three cusps of the valve attached to it. Above right and left aortic valve cusps in the aortic wall are origins of the right and left coronary arteries Interventricular Septum Thick wall between left and right ventricles. Has muscular and membranous part Margins of septum can be traced on surface of the heart by following the anterior and psoterior interventricular grooves Hydrostatic pressure of left ventricles causes muscular portion of septum to bulge toward right ventricle. Small, oval shaped membranous part of septum is thin and located inferior to cusps of aortic valve. Deoxygenated blood is delivered to heart through inferior and super venae cavae right atrium tricuspid valve orifice right ventricle--> pulmonic valve pumonary artery and lungs (CO2 released/oxygen absorbed) oxygen rich blood returns to heart through pulmonary veins left atrium mitral valve left ventricle aortic valve aorta distributed to all other tissues of the body. Impulse-Conducting System Main components of cardiac conduction system: sinoatrial node, atrioventricular node, bundle of His, right and left bundle branches, Purkinje fibers. Moderator band carries large portion of right bundle (IV, interventricular)l Impulse conducting system consists of specialized cells that initiate the heart beat and electrically coordinate contractions of the heart chambers. SA node is a small mass of specialized cardiac muscle fibers in wall of right atrium (located right of the superior vena cava entrance and normally initiates the electricl impulse for contraction) AV node is beneat the endocardium in inferiorposterior part of interatrial septum Bundle of His is distal to AV node perforates the interventricular septum posteriorly. Within septum, bundle of His bifurcates into a compact, cablelike structure on the right side, known as right bundle branch, and a broad sheet of fibers that continues over the left side of the septum, the left bundle branch. Right bundle branch is thick and deeply buried in muscle of interventricular septum and continues toward apex. Near junction of interventricular septum and anterior wall of right ventricle, right bundle branch becomes subendocardial and birfurcates One branch travels across right ventricular cavity in the moderator band, Other branch continues toward tip of ventricle. These branches evntually arborize into a finely divided anastomosing plexus that travels throughout right ventricle. Functionally, left bundle branch is divided into anterior and posterior fasciele and a small branch to septum. Anterior fascicle runs anteriorly toward apex, forming a subendocardial plexus in the area of anterior papillary muscle. Posterior fascicle travels to the area of the posterior papillary muscle It then divides into a subendocardial pleux and spreads to the rest of the left ventricle Subendocardial plexuses of both ventricles send distributing Purkinje fibers to the ventricular muscle. Impulses within the His-Purkinje system are transmitted first to the papillary muscles and then throughout the walls of the ventricles, allowing papillary muscle contraction to precede that of the ventricles. This coordination prevents regurgitation of blood flow through the AV valves. Cardiac Innervation Heart is innervated by both parasympathetic and sympathetic afferent and efferent nerves Preganglioninc sympathetic neurons, with cell bodies located within upper five to six thoracic levels of spinal cord, synapse with second-order neurons in the cervical sympathetic ganglia. Traveling within cardiac nerves, these fibers terminate in the heart and great vessels. Preganglioninc parasympathetic fibers orginiate in dorsal motor nucleus of medulla and pass as branches of the vagus nerve to the heart and great vessels. Here, fibers synapse with second-order neurons located in ganglia within these strutures. Rich supply of vagal afferents from inferior and posterior aspects of venctricles mediates important cardiac reflexes, whereas the abundant efferent fibers to the SA and AV nodes are active in modulating electrical impulse intiation and conduction Cardiac Vessels consist of coronary arteries and veins and the lymphatics Largest components of these structuers lie within the loose connective tissue in the epicardial fat. Coronary arteries Heart muscle is supplied with oxygen and nutrients by right and left coronary arteries, which arise from root of aorta just above aortic valve cusps After origin, they pass anteriorly, one on each side of the pulmonary artery. Large left main cornary artery passes between left atrium and pulmonary trunk to reach AV groove. It then divdes into left anterior descending (LAD) coronary artery and the circumflex artery. LAD travels within anterior interventricular groove toward cardiac apex. During its descent on anterior surface, the LAD gives off septal branches that supply the anterior two thirds of the interventricular septum and the apical portion of the anterior papillary muscle LAD also gives off diagnoal branhces that supply the anterior surface of left ventricle Circumflex artery continues within left AV groove and passes around left order of heart to reach the posterior surface Gives off large obtuse marginal branches that supply the laterla and posterior wall of left ventricle's Right coronary artery (RCA) travels in right AV groove, passing posteriorly between right atrium and ventricle. (perfuses the right venttricle and variable portions of the posterior left ventricle through its terminal branches) Posterior descending artery arises from RCA Supplies blood to right ventricle via acute marginal branhces. In most people, the distal RCA gives rise to a large branch, the posterior descending artery. Travels from inferoposterior aspect of heart tot he apex supplies blood to the inferior an dposterior walls of the ventricles and the posterior one third of the interventricular septum. Before posterior descnedin gbrnach, RCA gives off AV nodal artery. This vessel travels from inferoposterior aspect of heart to the apex and suppleis blood to inferior and posterior walls of the ventricles and the poterior one third of the interventricular septum Just before giving off posterior descneding branch, RCA usually gives off the AV nodal artery. Left main Coronary artery splits into circumfex artery and the anterior descneding artery Anterior descending artery: perfuses left ventricle anterior wall (anterior portion of the intraventricular septum and a portion of the anterior right ventricular wall) Circumflex artery: Perfuses the lateral and psoterior regions of the left ventricle Posterior descending and AV nodal arteries come from Right coronary artery in 85% of population Right dominant population 8% posterior descending artery comes from circumfex artery instead Left dominant circulation Remaining 7%, posterior blood supply comes from both RCA and circumflex Codominant circulation Blood supply to SA node (70% of time) comes from RCA 25% of normal hearts, SA nodal artery comes from circu flex artery 5% of cases, both RCA and circumflex artery contribute to SA nodal artery From epicardial locations, coronary arteries send perforating branches into ventricular muscle (richly vascularizes all chambers Capillaries arise from this that surround each cardiac muscle fiber Thesbesian veins (tiny vascular channels) or directly from terminal branches of coronary arteries supply muscle fibers just beneath endocardium (mostly papillary muscles and thick left ventricle) Collateral connections (less than 200 micrometer in diameter) exist at subarteriolar level between coronary arteries Become larger and visible in atheroscleorotic disease Coronary Veins Return blood from myocardial capillaries to right atrium via coronary sinus. Major veins lie in epicardial fat (superficial to arterial counterparts) Thesbesian veins provide alternative route for small amount of blood return to cardiac chambers. Lymphatic Vessels Heart lymph drained by vessels in subendocardial connective tissue of all four chambers. Drains into epicardial plexus (larger lymphatic vessels derive from this...follow coronary arteries and veins). Each larger vessels combines in AV groove to form single lymphatic conduit -->exits heart mediastinal lymphatic plexus thoracic duct. Histology of Ventricular Myocardial cells Myocyte = Mature myocardial cell ~ 25 micrometer in diameter; 100 micrometer in length Cross striated banding pattern like skeletal muscle Unlike skeletal muscle, contain only one or two centrally located nuclei Surrounded by connective tissue with rich capillary network Myocardial cells contain myofibrils: long chains of individual sarcomeres (fundamental contractile units of cell) Sarcomere: two groups of overlapping filaments of contractile proteins Myofilaments of myofibrils biochemically/physically interact muscle contraction Sarcomere produce cross-striated bandign pattern Density indicates concentration of contractile proteins Sarcomere length: Z to Z distance ~ 2.2 and 1.5 micrometers during cardiac cycle Larger dimension: ventricular filling Smaller dimension: ventricular contraction Figure 1.8 Myocardial cell Multiple parallel myofibrils surrounded by mitochondria T-tubules (invaginations of cell membrane the sarcolemme) increases surface area for ion transport and transmission of electrical impulses Intracellular SR has most of calcium, abuts the T tubules Sarcomeres Myofibril = serially connected sarcomeres extend from one Z line to next Composed of alternating (thin actin) and thick myosin myofilaments Titin tetheres myosin to Z line and provides elasticity Sarcolemma: myocardial cell membrane Specialized area in membrane: intercalated disk -distinct characteristic of cardiac muscle tissue Seen as dark staining transverse lines that cross chains of cardiac cells at irregular intervals represent gap junctions between cells; establishes structural and electrical continuity between myocardial cells. Transverse tubular system another functional feature of cell membrane of myocardial cell Deep fingerlike invaginations of sarcolemma Also establish pathways for rapid transmission of electrical signals for contractions Increases surface area of sarcolemma in contact with extracellular environment (allows transmembrane ion transport that occurs with excitationa nd relaxation to occur quickly and in sync). SR (Sarcoplasmic reiculum tubular membrane network complements T tubule system SR abuts T tubules at right angles in lateral sacs (terminal cisternae) terminal cisternae store calcium; release of stores links membrane excitation with activation of contractile apparatus Also abut lateral sacs and sarcolemma 35% of myocardial volume is mitochondria in order to sufficiently power heart cells. Basic Electrophysiology 3 electrophysiologic types Pacemaker cells (SA and AV node) Ventricular and Atrial muscle cells Specialized rapidly conducting tissues (Purkinje fibers) Sarcolemma (membrane) of these three electrophysiologic types: phospholipid bilayer (largely impermeable to ions) Membrane proteins (ion channels, passive cotransporters, active transporters) = maintain voltage difference. Ca++ and Na++ are mostly outside cell, Potassium is mostly inside cell Ion Movement and Channels Passive movement of ions depends on Energetic favorability Permeability of membrane for the ion Energetics Concentration gradient and transmembrane potential (voltage) drive passive ion flux. i.e. 145 mM Na++ outside; 14 mM Na++ inside...Na goes from high to low Transmembrane potential of myocyte ~ -90mV (so Na+ is attracted to inside negative charge). Permeability Voltage determines how many channels are open at a given time ~ voltage determines permeability voltage sensitive i.e. Fast sodium channel: transmembrane protein assumes various conformations based on voltage Open state only occurs for few thousandths of second Slow depolarization of cardiac fast sodium channels (and constant membrane that is less negative than usual ~ -70 mV). inactivation of channels occurs without initial opening and current flow Closed inactive channels cannot recover to resting state typical case in SA/AV nodes (fast sodium channels persistnetly unable to conduct Na+ ions). This is why sodium channels do not play a role in SA/AV nodes Potassiium and Calcium channels are also voltage sensitive, but behave differently than sodium channels (channel closed; inactivation gate open channel open; inactivation gate open channel open; inactivation gate closed) Figure 1-10: ion channels, cotransporters, active transporters of myocyte Sodium entry responsible for action potential in non pacemaker cells Calcium channels effective in phase 2 of purkinje fibers and muscle cells AP Potassium exits to repolarize cell; open potassium channels resting membrane potential of nonpacemaker cells sodium-calcium exchange protein keeps intracellular calcium low Sodium-potassium atpase maintains gradient for ion Active calcium tranporters remove calcim to external environment and into sarcoplasmic reticulum. Figure 1-11: Fast sodium channels 4 covalently linked transmembrane domains (I, II, III, IV) Resting Potential In nonpacemaker cells, electrical charge differential between inside and outside of cell = resting membrane potential Na K ATPase pump: 3 NA out, 2 K in--> keeps potassium ions high inside cell and sodium low Cardiac myocytes: Inward rectifier potassium channels open in resting state while other gates are closed (sodium and calcium). Cardiac myocytes are therefore more permeable to potassium. Potassium leaves, and causes cardiac myocytes to be highly negative inside. K eventually is re-attracted to highly negative interior: concentration gradient is opposed by electrostatic force.; at equilibrium they are equal and there is zero K + movement -26.7 ln (K in/ Kout) Action Potential Table 1-1 Transmembrane Cardiac Ionic Currents If Pacemaker current Responsible for phase 4 depolarization in pacemaker cells Ina Na++ current Responsible for phase 0 rapid depolarization in nonpacemaker cells Ica.L Slow, long lasting Ca++ current Responsible for phase 0 depolarization in pacemaker cells, major contributor to inward current during phase 2 of nonpacemaker cells Iki Maintain resting potential Current of inward rectifying potassium channel Ito Transient outward potassium current Responsible for phase 1 of action potential Iks, Ikr Delayed rectifier potassium currents of slow (Iks) and rapid (Ikr) types; repolarizing currents that are active during phases 2 and 3 of action potential. Cardiac Muscle cell Figure 1-13 Depolarization: Na+ (Ina) = rapid upstroke of phase 0 Transient outward potassium current (Ito) partial repolarization during phase 1 Slow Ca++ influx (Ica. I) balanced by K+ efflux (Ikl) = plateau of phase 2 Final rapid repolarization: from further K+ efflux phase 3 Phase 4 maintained by Ikl inward rectifier potassium channels Phase 4: resting state phase 0 At resting membrane, sodium/calcium channels are closed As voltage becomes more positive, more and more sodium channels open Sodium flows down concentration gradient as more channels open At threshold potential, enough of Na+ channels have opened generates self sustaining inward current that exceeds open rectifier potassium channels efflux Leads to rapid upstroke Sodium channel sopen for one thousandths of a second then quickly inactivated, which is why action potential is short lived. Phase 1 Brief current of repolarization returns membrane potential from positive to zero by transient outward potassium channels (Ito) phase 2 phase 3 phase Specialized conduction system Pacemaker cells Figure 1-14 Refractory Period Figure 1-15 Impulse Conduction Normal Sequence of Cardiac Depolarization Figure 1-16 Excitation-Contraction Coupling (electrical action potential leads to contraction of cardiac muscle cells....chemical energy in high phosphate bonds is translated into mechanical energy of myocyte contraction) Contractile Proteinsi n the Myocyte Main proteins: Myosin and Actin...regulated by troponin and tropomyosin Myosin Thick filaments ~ 300 molecules...globular heads evenly spaced. Contains myosin atpase (required for contraction) Actin smaller molecule (thin filaments alpha helix two strands that interdigitate between thick myosin filaments Titin Connects myosin to Z line of sarcomere; provides elasticity Tropomyosin double helix; lies in grooves between actin filmaments in resting state, ihibits myosin-actin interaction; prevents contraction during relaxed state Troponin Sits on actin filmaents three subunits (TnT); links troponin to actin and tropomyosin troponin I (TnI) inhibits ATPase activity of actin-myosin Troponin C (TnC) binds calcium ions that regulate contractile process Calcium-Induced Calcium-InducedRElease and the Contractile Cycle Calcium influx couples electrical activation to physical contractions phase 2 calcium influx by L-type Ca++ channels leads to small amount of calcium to enter This triggers Calcium release from sarcoplasmic reticulum T tubule invaginations of sarcolemal membrane l type channels close with specialized Calcium release receptors into SR (ryanodine receptors). When calcium binds ryanodine receptor, receptor open conformation much greater release of Calcium into cytosol from terminal cisternae of SR. This is called calcium induced calcium release (l type triggers calcium release from sarocplasmic reituclum) After larger calcium influx, calcium binds to troponin C (TnC) and allows contractions Calcium is sthen put back into sarcoplasmic reticulum via SERCA (sarcoendoplasmic reticulum calcium ATPASE). PL inhibits SERCA. When PL is dephosphorylated, it inhibits Calcium uptake. Excessive calcium released back into extracellular space via Sodium-calcium exchange Sarcolemmal Ca++ - ATPase (to a smaller degree). As calcium binds to TnC, TnI is inhibited; so it cannot inhibit actin-myosin interaction, which opens up active site between actin-myosin interface. Contraction: myosin heads bind to actin filaments and flex Cross bridge: When actin-myosin are together 1st step: activationof myosin head via hydrolysis of ATP (ADP + Pi + myosin head binds to actin) 2nd step: ADP + Pi + myosin head binds to actin formation of cross bridge conformation change of myosin head, pulls actin filament inward 3rd step: ADP is released, new ATP binds to mosin head, causing it to release actin filament Progressive coupling + uncoupling causes muscle fiber to shorten by increasing overlap between myofilaments within each sarcomere. As long as there is ATP, contraction continues as long as calcium concengtrationn is high to in order to bind TnC and prevent inhibition by tropomyosin Myocyte relaxation is also coupled with electrical activity Torward end of phase 2, L-type channels ianctivate arrests inlfuex of calcium, abolishes trigger for Calcium induced calcium release Calcium is pumped back into sarcoplasmic reticulum via Ca ++ ATPase (SERCA) Calcium is pumped outside by Na+ -Ca+ exchanger and to a lesser extent ATP-consumign calcium pump, sarcolemmal Ca++ - ATPase As calcium levels fall, Calcium dissociates from TnC, so tropomyosin is reactivated, and inhibts myosin-actin interface relaxation of contracted cell. Contraction-relaxation cycle repeats with next action potential. Introduction to Cardiac Signaling Systems Beta-Adrenergic and Cholinergic Signaling Concentration of Calcium in cytosol = major determinant of force of cardiac contraction with each heartbeat Beta-Adrenergic stimulation = enhances calcium fluxes in myocyte strengths fore of ventricular contractions Catecholamines (e.g. norepinephrine) bind to myocyte B1 adrenergic receptor Gstimulatory (inner surface of membrane ) membrane bound adenylate cyclase cAMP made from ATP cAMP activates PKA's phosphorylation of cellular proteins (i.e. L-type calcium channels) Increase in Calcium ions in sarcoplasmic reticulum increase in force of contractions B-adrenergic stimulation also enhances myocyte relaxation Phospholamban (PL) returns Ca++ to cytosol of SR SR membrane bound protein When dephosphorylyzed, PL inhibits Ca++ uptake by SR via SERCA However, Beta adrenergic activation of PKA inhibits PL's inhibitory effect Greater intake of Calcium ion increases Calcium removal from cytosol myocyte relxation Phosphorylation of TnI also due to increased cAMP activity (inhibits actin-myosin interaction further relxation of cell) Cholinergic Signaling (PNS from vagus nerve) opposes Beta-Adrenergic stimulation. Acetylcholine muscarinic M2 receptor G proteins Gi (G inhibitory) inhibits adenyl cyclase activity reduces cAMP At sinus node: heart rate decreases Myocardium: counteract force of contraction induced by beta-adrenergic signaling Ventricular cells are less sensitivity to cholinergic signaling than atrial cells (due to different degrees of G protein coupling) Basically, adrenergic receptor enhances contraction, while cholinergic opposes enhancement.