Download L01 Electrophysiology of Heart Cells

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
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- 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
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○ 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
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 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
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○ 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
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