Electrophysiology II

depolarization

phase of AP characterized by loss of polarization

MP becomes less negative

repolarization

phase of AP where polarization is reestablished

MP is increased as the inside of the cell becomes more negative

fast response AP

occur in the atrial and ventricular myocytes and Purkinje cells

phase 4 - RMP (fast)

membrane potential -90mV

K ion partitioning across the membrane is the primary determinant of the RMP

no net ion movement

phase 0 - rapid depolarization (fast)

stimulus from adjacent cells (small influx of + ions) reduces the MP (becomes less negative) enough to reach threshold (-65 to -70mV)

rapid influx of Na+ occurs through voltage-gated, fast Na channels

the interior of the cell rapidly becomes more positive

rate of phase 0 is key determinant of the cell to cell conduction velocity

events triggered when threshold is met

activation gate (m gate) of voltage-gated Na+ channels opens quickly

inactivation gate (h gate) of voltage-gated Na+ channels close slowly

voltage-gated K+ channel (Ikv) opens slowly

allows for rapid Na+ influx for a brief period

phase 1 - initial repolarization (fast)

initial repolarization via opening of K+ channels

K+ out of the cell

phase 2 - plateau (fast)

MP is relatively stable

combination of ion movements

• Na+ channels inactivated

• long acting Ca++ channels opened (Ca influx)

• K+ channels opened (K+ efflux)

phase 3 - completion of repolarization (fast)

K+ channels are fully activated and opened allowing for efflux of the K+ ions

MP is retuned to the RMP

fast response AP - summary of ion movements

4 - resting membrane potential

0 - depolarization

1 - initial repolarization

2 - plateau

3 - repolarization

slow response AP

occur in SA and AV nodes

phase 4 - RMP & spontaneous depolarization (slow)

less negative RMP of - 60mV

continuously drifting towards threshold of -40mV allowing for spontaneous depolarization of the pacemaker cells in the SA node

phase 0 - depolarization (slow)

slow upstroke via a slow influx of Ca+

why do you think slow response AP use Ca influx to depolarize instead of Na influx?

fast response Na channels need to be reset to the resting state to work (-90mV)

slow response APs RMP is -65mV, so most Na channels are inactivated

phase 3 - repolarization (slow)

K+ currents are responsible for repolarization - K+ channels open

as the inside of the cell becomes more (-) the MP is returned to RMP

slow response AP - summary of ion movement

4 - spontaneous diastolic depolarization

0 - full depolarization

3 - repolarization

automaticity and subsidiary pacemakers

nodal cells display automaticity and the SA node typically has the fastest depolarization rates (acts as pacemaker)

some other parts of the conducting system can also display automaticity and act as subsidiary pacemakers if the SA node fails to discharge

depolarization rates in subsidiary pacemakers

SA node - 70-160 bpm

AV node - 40-60 bpm

Purkinje fibers - 15-40 bpm

AP propagation

gap junctions allow ions to pass from a depolarized cell to the adjacent cell propagating the depolarization wave

refractory period (RP)

cells are unresponsive to restimulation

relative refractory period (RRP)

a stronger than normal stimulus from an adjacent cell can prematurely excite the cells

ventricular premature complexes (VPC)

an arrhythmia caused by abnormally early depolarization of ventricular cardiomyocytes

treatment - drugs that prolong the refractory period

Sotalol - blocks beta receptors and K+ channels

how would sotalol help to prevent the ventricular premature complex form occurring?

extend total/complete refractory period, so the stimulus falls in RP

how does serum hyperkalemia affect the AP

less negative RMP

slower depolarization (fewer Na+ channels available to open)

faster repolarization (more K+ channels open)

extracellular hyperkalemia effects on different tissues in the heart

sensitivity to hyperkalemic effects: atrial > ventricular myocytes > nodal tissues

in nodal tissues, hyperkalemia reduces the funny current and slows the rate of spontaneous phase 4 depolarization (mimics inc parasympathetic tone)

Which of the following AP events allows sinoatrial nodal cells to act as the pacemaker of the heart?

a. A slower depolarization during phase 0.

b. Spontaneous diastolic depolarization during phase 4.

c. A less negative resting membrane potential

d. the influx of Ca through the L-type calcium channel during phase 2.

B. Spontaneous diastolic depolarization during phase 4.