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L01 Electrophysiology of Heart Cells Tuesday, April 14, 2015 5:19 PM Sequence of Cardiac AP Conduction - SA Node -> Inernodal fibers -> AV Node -> Atrial tissue -> Bundle of HIS -> R + & Bundle Branches -> Purkinje Fibers -> Myocytes Normal Sinus rhythm = 60-100 bpm Sinus tachycardia -> originates in Sinus node and is 100+ bpm - Caused by exercise/hypovolemia Sinus bradycardia -> originates in sinus node and is <60 bpm - Caused by exercise training, hypothermia, and medication Ions and Channels for AP - Resting membrane potential is -90 mV - K+ concentration is high INSIDE the cell -> primarily determines resting potential - Na/K ATPase maintains high concentration of K inside and high Na outside - Various ion channels include ○ Na+ Channel opening to allow rush of Na inside ○ Fast K+ channel and Delated K+ Channels allowing K to leave ○ L-type Ca+ channel allowing Ca+ to enter cell ○ HCN Channel = Hyperpolarization Activated Cyclic Nucleotide gated channels As membrane hyperpolzarizes, channel activates in presence of cAMP and allows Na to enter/K to leave 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 Funny Current - Autorhythmic cells generate action potental spontaneously WITHOUT input from nervous system due to unstable resting potentional = Pacemaker potential ○ Cells show gradual depolarization until reaches threshold -> AP produced ○ Ionic current responsible for this unstable resting potential = Funny Current - During phase 4, influx of Na and Efflux of K+ but there is a greater influx of Na than K via HCN Physio Page 1 - During phase 4, influx of Na and Efflux of K+ but there is a greater influx of Na than K via HCN Channels ○ Near end of Phase 4, Transient (T-type) Ca+ channels open and allow passage of Ca+ ○ CLINCAL Ivabradine inhibits HCN channels and slows down Na+ influx => takes longer to reach threshold => PURE HR REDUCTION (NO FX ON CONTRACTILITY) - During Depolarization (Phase 0), Ca+ comes in via Long channels - Phase 3 -> membrane channels become more positive and K+ efflux through Delayed Rectifier channels Autonomic Innervation of Heart - Sympathetic innervation ○ Cardiac sympathetic nerves release Nor-Epi => INCREASE HR ○ RIGHT cardiac nerve -> SA NODE -> INCREASES CHRONOTROPICITY (HR) NE acts on Beta-1 receptors on SA NODE cells -> increases cAMP production => increases HCN activity => increasing rate of spontaneous depolarization => INCREASE IN HR □ cAMP also causes earlier opening of L-type Ca+ Channels ○ LEFT Cardiac nerve -> AV NODE -> INCREASES DROMOTOPICITY (CONDUCTION) ALSO LEFT VENTRICLE -> INCREAES IONOTROPICITY (CONTRACTION) - Parasympathetic innervation ○ Vagus nerve releases ACh => DECREASE HR ○ RIGHT Vagus -> SA NODE -> DECREASE CHRONOTOPICITY ACh acts on M2 receptors on SA NODE cells -> Decreases cAMP production => decreases HCN activity and delays L-type Ca+ opening => decreases spontaneous depolarization rate => DECREASES HR M2 receptor also activates K+ channel causing hyperpolarization CLINICAL □ Atropine blocks M2 receptor thus decrease parasympathetic effect ○ LEFT Vagus -> AV NODE -> DECREASES DROMOTROPICITY AV Node - AV node slows down conduction from SA Node to ensure adequate filling of ventricles during diastole - AV node, bundle of his, and purkinje fiber cells re referred to as LATENT PACEMAKERS SA Node cells have the fastest phase 4 depolarization so they set the pace = OVERDRIVE Physio Page 2 ○ SA Node cells have the fastest phase 4 depolarization so they set the pace = OVERDRIVE SUPRESSION ○ If Latent pacemaker takes over and becomes pacemaker -> ECTOPIC FOCUS - CLINCAL ○ 1st Degree AV Block Prolongs AV node conduction to >0.2 seconds (Prolonged PR Interval) Commonly caused by enhanced vagal tone ○ 2nd Degree AV Block Some AV node conduction occurs but others are dropped (Some absent QRS) Caused by Excessive vagal tone; ischemia/MI ○ 3rd Degree AV Block ALL AV node conduction is BLOCKED (P-P interval is shorter than R-R intervals) □ Still see QRS because Ventricular rhythm is set by junctional/ventricular escape rhythm □ Intervals have difference because the Atrial rhythm is set apart from the ventricular rhythm Caused by Ischemia/MI Treat with Pacemaker ○ Atrial Fibrillation Multiple foci discharge in atria causing fast and irregular atrial contractions EKG shows no P-wave but instead a jumble before QRS and IRREGULAR R-R Intervals The rapid impulse rate does not get conducted to ventricles because AV node cells slow down conduction and Ventricles have their own refractory period ○ Wolf-Parkinson-White Syndrome An aberrant pathway exists which causes pre-excitation, or early depolarization of the ventricles (instead of going through AV Node) In WPW Syndrome, the pathway is the Bundle of Kent and EKG will show Delta wave = decreased P-R interval due to SLOW rise of QRS spike Heart Cells - Heart contains ○ Conducting Cells = function is to rapidly spread AP over myocardium Exhibit Automaticity = ability to spontaneously generate AP without neural input Exhibit Rhythmicity = ability to generate AP in regular, repetitive manner Have more positive but unstable membrane potential Do not have any plateau ○ Contractile Cells Cardiac myocytes are connected by intercalated disks with Desmosomes and Gap junctions ○ Desmosomes -> link myocytes mechanically to allow simultaneous contraction/relaxation ○ Gap junctions -> link myocytes electro-chemically to allow instantaneous AP transfer and allows myocardium to behave as a FUNCTIONAL SYNCYTIUM Longer duration AP with Plateau Have stable resting membrane potentials Physio Page 3 Have stable resting membrane potentials ○ H-gate Closure at phase 1,2,3 is responsible for ABSOLUTE REFRACTORY PERIOD H-gate opens during late repolarization = Relative Refractory period -> prevents against Tatanic contraction - CLINICAL ○ Normal ventricular contraction occurs when purkinje fiber sends conduction that splits and AP would cancel each other out when wrapping back ○ However, a partial conduction block (caused by ischemia or plaque) can prevent normal conductance and wrapping -> previously contracted cells in refractory period may fire AP again Physio Page 4 ○ Antiarrhythmic drugs alter absolute refractory period/conduction velocity to prevent reentry Class 1a agents block FAST Na+ Channels => blocks channels from opening so depolarization takes longer and absolute refractory period EXTENDS/Conductance decreases Class 3 agents block K+ channels => preventing repolarization and refractory period extends Physio Page 5