BME 501 Advanced Topics in Biomedical Systems Spring 2014 Dr. KayBME 501 Lecture Notes – Apr 7 Electrical Activity of Cardiac Cycle • SA Node • AV Node • Electrical Conduction • Regulation of Cardiac APs • Introduction to ElectrocardiogramSA Node AV Node Contraction Cycle in Heart Ventricular diastole: • Ventricles at rest, fill with blood Atrial systole: • Atria push additional blood into ventricles during ventricular diastole Ventricular systole: • Blood ejected from ventricles • Atria in diastole, refill with bloodSinoatrial (SA) Node • Properties intrinsic to cardiac tissue - Automaticity: ability of heart to initiate its own beat - Rhythmicity: regularity of pace-making activity • Cardiac function does not require intact nervous pathways • SA node: natural pacemaker of heart • Cells in SA node generate impulses spontaneously • Two or three additional sites of automaticity near SA node complete atrial pacemaker complexSinoatrial (SA) Node • Contains two principal cell types: - Round cells (pacemaker cells) - Spindle-shaped transitional cells (conduct impulses within node and to nodal margins) • Typical AP in SA node (slow response) vs. ventricular myocardial cell (fast response): - Peak lesser in magnitude - Upstroke (phase 0) less steep - Lack phase 1 - Plateau (phase 2) not as sustained - Repolarization (phase 3) more gradual • Nodal cells lack iKir (inward rectifying current), causing resting Vm to be less negative than in atrial or ventricular myocytesSinoatrial (SA) Node • Function of fast Na+ channels suppressed in SA node cells • Tetrodotoxin (TTX) has no influence on AP in SA node • Blockage of Ca2+ channels by nifedipine or verapamil does suppress AP generation in primary SA node cellsSinoatrial (SA) Node • SA node cells differ from non-automatic cells in their phase 4 behavior • Slow depolarization occurs throughout phase 4: pacemaker potential • Depolarization proceeds at steady rate until a threshold is attained, then AP is triggered • Frequency of pacemaker-cell discharge affected by - Rate of phase 4 depolarization - Maximal negativity at end of repolarization - Level of threshold potentialSinoatrial (SA) Node • Multiple ionic currents contribute to slow depolarization during phase 4 - Inward current (funny current, if); carried mostly by Na+, only active at negative potentials up to about –50 mV - 3Na+-1Ca2+ exchanger generates inward current iNa-Ca that contributes substantially to pacemaker depolarization - When membrane potential becomes less negative than –55 mV, inward current of Ca2+ contributes to depolarization (voltage-activated T- and L-type Ca2+ channels) - Outward iK from delayed rectifier channel (KV) decays with time, decreasing polarizing/repolarizing K+ current • Node APs are small in amplitude, slow-rising • Node APs generated solely by an inward Ca2+ currentSinoatrial (SA) NodeAtrioventricular (AV) Node • Located in posteroinferior region of interatrial septum • Part of electrical control system of heart that coordinates top and bottom of heart • Conducts electrical impulses from atria to ventricles (only electrical connection across annulus fibrosus) • Has similar ion currents to SA node cells (both contain slow-response cells) • Delays impulse from atria by approximately one-tenth of a second (100 ms) • Delay very important: - Ensures atria have ejected their blood into ventricles before ventricles contract - Protects ventricles from excessively fast rate response to atrial arrhythmias• SA node – Initiates electrical activity (unstable membrane potential; spontaneous firing of APs approximately once every second) – Rapid propagation: ~1 meters/second (m/s) • AV node – Conducts electrical impulse from atria to ventricles – Complex local circuitry and small diameter of nodal cells (2 to 3 μm) delay electrical impulse – Slows conduction velocity to ~0.05 m/s Electrical Conduction• Bundle of His – Conveys electrical impulse from AV node to ventricles – Divides into left and right bundle branches • Purkinje fibers – Bundle branches terminate in extensive network of large fibers in subendothelium: Purkinje fibers – Widest cells in heart (40 to 80 μm in diameter) – Rapid conduction velocity: ~3 to 5 m/s – Distribute electrical impulse rapidly to subendocardial myocytes – Impulse then travels from myocyte to myocyte, generally outward toward epicardium, at ~0.5 to 1 m/s Electrical ConductionElectrical ConductionPacing Redundancy • Fastest pacemaker (in SA node) dominates hierarchy of slower, latent pacemakers • In absence of atrial pacemaker complex, AV node usually becomes pacemaker for entire heart • When AV junction unable to conduct impulse from atria to ventricles - Idioventricular pacemakers in Purkinje fiber network initiate ventricular excitation and contractions - Purkinje fibers fire at a very slow rate; typically 30 to 40 BPM - Usually insufficient to pump adequate CO• Parasympathetic stimulation produces slow HR (bradycardia) through release of acetylcholine – Increases K+ conductance controlled by cholinergic receptors (iK,Ach), causing hyperpolarization of cell membrane (Vm approaches EK) – Decreases phase 4 depolarizing currents if (carried by Na+) and iCa (carried through L-type Ca2+ channels) • Parasympathetic inhibitory effect predominates at rest Regulation of Cardiac APs: Physiological Brief vagal stimulus• Sympathetic stimulation produces increased HR (tachycardia), contractility, and relaxation rate through release of noradrenaline – Noradrenaline and circulating adrenaline (catecholamines) activates cardiac β1-adrenoceptors – β1-adrenoceptors activate cAMP-PKA pathway – cAMP increases open-state probability of if channels – PKA catalyzes phosphorylation of L-type Ca2+ channels, increasing open state probability and duration Regulation of Cardiac APs: Physiological– PKA phosphorylates slow/delayed rectifier K+ channels, increasing outward/repolarizing current iKv; shortens length of AP – PKA phosphorylates phospholamban, releasing Ca2+ pump on SR from inhibition; boosts Ca2+ transfer from sarcoplasm into SR and speeds relaxation of muscle fibers – β1-adrenoceptor activation may cause phosphorylation of Ca2+ release channels on SR, increasing fraction of Ca2+ released from intracellular store per excitation Regulation of Cardiac APs: Physiological• Temperature affects heart