Lecture 12 Introduction to the Cardiovascular System_2023 study guide based only.pdf

Cardiomyocyte Characteristics Objective 2 2 Types of Cardiac Muscle Cells Contractile Cells Conducting Cells (specialized) Where?- Majority of atrial and ventricular tissue Where? – Sinoatrial node (SA node), atrial internodal tracts, Atrioventricular node (AV node), the bundle of His and the P...

Cardiomyocyte Characteristics Objective 2 2 Types of Cardiac Muscle Cells Contractile Cells Conducting Cells (specialized) Where?- Majority of atrial and ventricular tissue Where? – Sinoatrial node (SA node), atrial internodal tracts, Atrioventricular node (AV node), the bundle of His and the Purkinje system Function: Working cells of the heart • Action potentials lead to muscle contraction, which generates of force for pumping blood. Function: Rapidly spread action potentials • Do not contribute to generation of force ** Capacity to generate action potentials spontaneously (normally suppressed except for SA node) 7 Cardiomyocyte Characteristics Objective 2 (SA node = “sinoatrial” node) Figure 14-17 from Silverthorn’s Human Physiology 5th ed 8 Cardiomyocyte Characteristics Objective 2 Intercalated Disks Link Adjacent Cardiac Myocytes Mechanically and Electrically Gap Junction Latticework of cells = syncytium* Cells are “synced” into one operating unit Heart is composed of two syncytiums: Atrial syncytium Ventricular syncytium As such, the atria work as a coordinated unit and the ventricles work as a coordinated unit Gap junctions link adjacent myocytes electro-chemically Allows sequential action of atria first followed by ventricles second, producing coordinated, unidirectional movement of blood. *pronounced “sihn-si-shee-uhm” 9 Origin and Spread of Excitation in the Heart Bachmann's Bundle Objective 3 Sequence of cardiac action potential 1. SA (sinoatrial) Node – initiation of action potential, pacemaker 2. Atrial internodal tracts and atria – tracts carry action potential to right and left atria 3. AV (atrioventricular) node – action potential from right and left atria simultaneously conduct to AV node. **Slow conduction velocity 4. Bundle of His, Purkinje fibers, and ventricles – from the AV node, the action potential enters the His-purkinje system of the ventricles **Fast conduction velocity Fibrous tissue between the atria and ventricles are characterized by high electrical resistance such that myocardial action potential propagated from the atrial syncytium to the ventricular syncytium has to go through the specialized conduction system called the AV node (atrioventricular (AV) bundle). 10 Conduction Velocity Conduction velocity is the speed at which action potentials propagate within the tissue measured in meters per second (m/sec) • Slowest in AV node (0.01 to 0.05 m/sec) • Fastest in the Purkinje fibers (2 to 4 m/sec) • Conduction through AV node (AV delay) requires almost ½ of total conduction time (100msec) Objective 4 Timing of activation of the myocardium Why is conduction velocity important? … implications for physiologic functions Slow conduction velocity of AV node ensures ventricles do not activate too early (i.e. before they have time to fill with blood from atria) Rapid conduction velocity of Purkinje fibers ensures ventricles are activated quickly in a smooth sequence for the efficient ejection of blood. The numbers superimposed on the myocardium indicate the cumulative time, in m/sec, from the initiation of the action potential in the SA node (time 0). 11 Objective 5 Ions and Ion Channels Involved in Cardiac Action Potentials Resting Ventricular Myocyte K+ (150 mM) -90 mV Na+ (20 mM) Ca2+ (0.0001 mM) • • • K+ (4 mM) Na+ Equilibrim Potential -94 mV +70 mV (145 mM) Ca2+ (2.5 mM) +132 mV Resting membrane is determined primarily by K+ Na+-K+ ATPase maintains gradients across the cell Changes in membrane potential are caused by the flow of ions into or out of the cell which results from: • Changes in the electrochemical gradient for a permeant ion • Changes in conductance of an ion HCN channel- hyperpolarization-activated cyclic nucleotide-gated channel Figure 17-5 from Preston and Wilson’s Physiology 13 Objective 6 Sinoatrial (SA) and Atrioventricular (AV) nodes SLOW +20 0 -20 0 -40 -60 3 4 -80 -100 100 msec • • • • Exhibit automaticity More positive resting membrane potential Unstable resting membrane potential No sustained plateau Membrane Potential (mV) Membrane Potential (mV) Cardiac Action Potentials Atrial, ventricular and Purkinje fibers FAST +20 1 2 0 -20 -40 0 3 -60 -80 4 -100 100 msec • • • Long duration (150-250 msec) Stable resting membrane potential (~-85mV) Plateau 14 Action Potentials in the SA and AV node SA Node = natural pacemaker of the heart Features of SA Node Action Potentials • Automaticity: generate action potentials spontaneously without neural input - caused by pacemaker potential • Unstable resting membrane potential “pacemaker potential” - Notice region 4 not flat • No sustained plateau - No discernable phase 2 Objective 6 +20 0 -20 -40 Threshold -60 -80 -100 Pacemaker potential Action potential Time (msec) 15 Action Potentials in the SA and AV Node Phase 0 – Upstroke • ↑Ca2+ entry into SA cells … inward Ca2+ current (primarily “Transient” (or T-type) Ca2+ channels Phase 3 – Repolarization • ↑ K+ exits cells … outward K+ current Phase 4 – Spontaneous depolarization or “pacemaker potential” • HCN Channels – hyperpolarization-activated cyclic nucleotide gated channels. OPEN as Vm approaches -65 mV. • Maximum diastolic potential = ~ -65 mV • Opening of Na+ channels and inward Na+ current called If (‘f’ stands for funny) creates slow depolarization • If is turned on by repolarization from the preceding action potential (ensures each AP in the SA node will be followed by another AP) • Once If brings the potential to the threshold, T-type Ca2+ channels open for the upstroke NOTE: Rate of phase 4 depolarization sets the heart rate: modified by agents that affect heart rate. Objective 5, 6 +20 0 ICa 0 -20 -40 IK 3 “funny current” -60 -80 If 4 Threshold Pacemaker potential Action potential Time (msec) -100 K+ outside inside Na+ (HCN channel) Ca2+ (L) 16 Objective 5, 6 Action Potential in the Atria, Ventricles, and Purkinje Fibers Phase 0 - upstroke • Rapid depolarization caused by ↑in Na+ conductance (gNa) produced by depolarization-induced opening of activation gates on Na+ channels • ↑ gNa causes inward Na+ current INa • Drives membrane potential towards Na+ equilibrium of ~+65 mV ICa INa • At peak of upstroke, membrane potential is depolarized to ~ +20mV Phase 1 – initial repolarization • Brief period of repolarization following upstroke • Inactivation gates to Na+ channels close… ↓gNa…inward INa ceases • Net outward current of K+ down electrochemical gradient IK IK 1 Phase 2 - plateau • Stable depolarized membrane potential (shorter in atrial fibers) caused by no net current flow across the membrane • ↑ gCa.. Inward ICa (slow- L-type) • Outward IK driven by electrochemical gradient 18 Objective 5, 6 Action Potential in the Atria, Ventricles, and Purkinje Fibers Phase 3 - repolarization • Outward currents are greater than inward currents • ↓ gCa …↓ inward Ca2+ current (ICa) • ↑gK … ↑ outward K+ current (IK) down steep electrochemical gradient • At the end of phase 3, outward IK is reduced because repolarization brings membrane potential closer to EK (↓driving force) ICa INa IK IK 1 Phase 4 – resting membrane potential • Return resting level of ~ -90 mV • Inward and outward currents are equal • K+ channels and current responsible for phase 4 are different from those responsible for repolarization (phase 3) , therefore conductance is gK1 and current is IK1 • High gK1 … outward IK1 • Outward current is balanced by inward current of Na+ and Ca2+ maintained by Na+-K+ ATPase and Na+-Ca2+ exchanger 19 Autonomic Effects on Heart Rate Sympathetic • cardiac sympathetic nerves release norepinephrine which ­ heart rate Right Parasympathetic nerves (vagi) • The right cardiac nerve dominates the SA node and impacts heart rate (chronotropicity) • The left cardiac nerve dominates innervation of the left ventricle, and effects contractility (inotropicity) Cardiac sympathetic nerves Objective 8 Parasympathetic Left • Vagus nerves release acetylcholine which ¯ heart rate • The right vagus dominates the SA node and impacts HR (chronotropicity) • The left vagus dominates the AV node and impacts conduction velocity (dromotropicity) Figure 9-12 from Guyton and Hall’s Textbook of Medical Physiology 12th ed 22 Introduction: Autonomic Effects of Heart and Blood Vessels 23 Sympathetic Nerves Increase Heart Rate Objective 8 Increased rate of depolarization • Norepinephrine (NE) acts at β1-adrenergic receptors on SA Nodal cells. – – • • • • Receptor à G-protein à adenyate cyclase à increased cAMP cAMP binding to HCN hyperpolarization activated cyclic nucleotide gated) channel increases channel opening = faster depolarization. ­ the If thereby increasing the rate of spontaneous depolarization. ↑ Ica … more functional L-type Ca2+ channels… less depolarization to reach threshold In sum, NE ­gNa+, ­gCa2+, ­ gK+ Heart rate increases SA Nodal Action Potential 0 * mV -40 -60 Time *Positive chronotropic effects of sympathetic nerve activation 24 Objective 8 Parasympathetic Nerves Decrease Heart Rate – cAMP levels drop, HCN channel opens less • ↓If • ¯ If decreases the rate of spontaneous depolarization to threshold. • Delays opening of L-type calcium channels • Heart rate decreases SA Nodal Action Potential Membrane potential (mV) Decreased rate of depolarization • Acetylcholine acts at Muscarinic M2 receptors on SA Nodal cells. (2 effects) • M2 receptors are coupled to GK that inhibits adenylyl cyclase… 20 0 * * -20 -40 -60 -80 Time *Negative chronotropic effects of parasympathetic nerve activation 25 Objective 8 Parasympathetic Nerves Decrease Heart Rate SA Nodal Action Potential Membrane potential (mV) Negative shift in the maximum diastolic potential • Gk directly increases the conductance of K+ channel called K+-ACh and increases outward K+ current (IK-ACh) • K+ exits nodal cells causing them to hyperpolarize the maximum diastolic potential • Threshold potential increases b/c ↓ ICa • Heart rate decreases 20 0 * * -20 -40 -60 -80 Time * Negative shift in maximum diastolic potential with activation of the parasympathetic nerve activation 26 Electrocardiogram (ECG or EKG) • • • Objective 9 Various waves represent depolarization or repolarization of different portions of the myocardium and are given lettered names. Intervals and segments between the waves are also named. Intervals include waves, segments do not include waves Recall: The entire myocardium is not depolarized at once. The result of the sequence and timing of depolarization and repolarization establishes potential differences between different parts of the heart that can be detected by electrodes. 28 Electrocardiogram (ECG) Objective 9 • P wave – Depolarization of the atria – Duration correlates with conduction time through atria – Does not include atrial repolarization, which is “buried” in the QRS complex • PR interval (P wave + PR segment) – Time from initial depolarization of the atria to initial depolarization of the ventricles – PR segment – an isoelectric flat portion of ECG that corresponds to AV node conduction – PR interval is normally 160 milliseconds • ↑ conduction velocity through AV node ↓ PR interval • ↓ conduction velocity through AV node ↑ PR interval 29 Electrocardiogram (ECG) Objective 9 • QRS Complex (3 waves- Q,R,& S) – Collectively represent depolarization of the ventricles (normally < 120msec) • T wave – Repolarization of the ventricles • QT interval (QRS complex + ST segment + T wave) – Represents the first ventricular depolarization to last ventricular repolarization – ST segment is an isoelectric portion of the QT interval that correlates with the plateau of the ventricular action potential 30