Lecture #22: Physiology: Cardiac Action Potentials

What are the two types of cardiac action potentials?

Fast-response action potentials and slow-response action potentials.

Which cardiac cells have fast-response action potentials?

Ordinary working atrial and ventricular myocytes and the His-Purkinje conduction system have fast-response action potentials.

Which cardiac cells have slow-response action potentials?

Pacemaker cells of the specialized cardiac pacing/conduction system, particularly the SA and AV nodes, have slow-response action potentials.

What distinguishes the phase 0 upstroke of fast vs slow response APs?

Fast-response phase 0 results from opening of voltage-gated Na+ channels and has a rapid upstroke (>100 V/s). Slow-response phase 0 results from opening of L-type Ca2+ channels and has a slower upstroke (~10 V/s).

What are the 3 major ions involved in cardiac action potentials?

K+, Na+, and Ca2+. Their concentration gradients and the membrane's relative permeability to each ion are major determinants of the cardiac action potential.

What are the major mechanisms that maintain cardiac electrolyte homeostasis?

Na+/K+ ATPase, Na+/Ca2+ exchanger, and Ca2+-ATPase/SERCA maintain ion gradients and intracellular Ca2+ homeostasis.

What is the stoichiometry of the Na+/K+ ATPase?

The Na+/K+ ATPase transports 3 Na+ across the membrane for every 2 K+ transported in the opposite direction.

What is the stoichiometry of the Na+/Ca2+ exchanger?

The Na+/Ca2+ exchanger operates with a 3:1 Na+:Ca2+ ratio.

What are the approximate equilibrium potentials for K+, Na+, and Ca2+ given in the lecture?

EK ≈ -96 mV, ENa ≈ +52 mV, and ECa ≈ +134 mV.

How many phases are in a fast-response cardiac action potential?

Five phases: phase 0, phase 1, phase 2, phase 3, and phase 4.

What causes phase 0 of the fast-response AP?

Rapid opening of voltage-gated Na+ channels causes Na+ influx, producing rapid depolarization with a high dV/dt.

What happens to voltage-gated Na+ channels during the fast-response AP?

At rest the channels are available for activation; during phase 0 they rapidly activate and conduct Na+; after depolarization they become inactivated and cannot immediately reopen until the membrane repolarizes sufficiently for recovery.

What causes phase 1 of the fast-response AP?

Phase 1 is early/initial repolarization caused by inactivation of voltage-gated Na+ channels and opening of transient outward K+ channels, producing K+ efflux.

What is the major K+ current involved in phase 1?

The transient outward K+ current, IKto.

What causes the phase 2 plateau of the fast-response AP?

Ca2+ influx through L-type voltage-gated Ca2+ channels is balanced by K+ efflux through delayed rectifier K+ channels, producing the plateau.

What Ca2+ current is important during phase 2?

The L-type Ca2+ current, ICa(L), provides inward Ca2+ current during the plateau.

What K+ currents contribute to the phase 2 plateau?

Delayed rectifier K+ currents, including IKr, IKs, and IKur, contribute outward K+ current that opposes inward Ca2+ current.

Why does phase 2 remain near a plateau instead of rapidly depolarizing or repolarizing?

Inward Ca2+ current through L-type Ca2+ channels is approximately balanced by outward K+ current, maintaining membrane potential near the plateau.

What causes phase 3 of the fast-response AP?

Phase 3 is rapid repolarization caused predominantly by outward K+ currents as Ca2+ channels close and K+ conductance dominates.

Which K+ channels contribute to phase 3 repolarization?

Delayed rectifier K+ channels and inward-rectifying K+ channels, particularly IK1, contribute to phase 3.

What characterizes phase 4 of a ventricular fast-response AP?

Phase 4 is a stable resting membrane potential near -90 mV with high K+ permeability. Ion pumps and exchangers restore and maintain electrolyte homeostasis.

What are the two major functions occurring during phase 4 of a fast-response AP?

Maintenance of the resting membrane potential and restoration of electrolyte homeostasis.

What is the high-yield sequence of fast-response AP phases?

Phase 0 = rapid Na+ depolarization; phase 1 = initial K+ repolarization; phase 2 = Ca2+ influx balanced by K+ efflux; phase 3 = K+-mediated rapid repolarization; phase 4 = stable K+-dependent resting potential.

How many phases are present in a slow-response pacemaker action potential?

Three phases: phase 0, phase 3, and phase 4. Pacemaker cells do not have the distinct phases 1 and 2 seen in fast-response cells.

What causes phase 0 of a slow-response AP?

Opening of L-type Ca2+ channels causes Ca2+ influx and the slow phase 0 depolarization.

Why is phase 0 slower in pacemaker cells than in ventricular myocytes?

Pacemaker phase 0 depends on slower L-type Ca2+ channels rather than the fast voltage-gated Na+ channels responsible for ventricular phase 0.

What causes phase 3 of the slow-response AP?

Opening of K+ channels produces K+ efflux and repolarization.

Why do pacemaker cells lack a true resting membrane potential?

During phase 4, pacemaker cells undergo spontaneous depolarization rather than remaining at a stable resting membrane potential.

What currents contribute to spontaneous phase 4 depolarization in pacemaker cells?

The pacemaker or funny current (If), deactivation of IK1, and T-type Ca2+ current contribute to spontaneous phase 4 depolarization.

What is the funny current (If)?

If is a hyperpolarization-activated, nonselective cation or pacemaker current consisting of a mixed inward Na+/K+ current that contributes to spontaneous phase 4 depolarization.

What is the role of T-type Ca2+ channels in pacemaker cells?

T-type Ca2+ current contributes to spontaneous phase 4 depolarization toward threshold.

What are the major components of cardiac excitation-contraction coupling emphasized in the lecture?

L-type Ca2+ channels/dihydropyridine receptors, ryanodine receptors, calcium-induced calcium release (CICR), and SERCA are key components.

What initiates cardiac excitation-contraction coupling?

Depolarization activates L-type Ca2+ channels, also called dihydropyridine receptors, allowing Ca2+ to enter the cardiac myocyte.

What is calcium-induced calcium release (CICR)?

Ca2+ entering through L-type Ca2+ channels triggers ryanodine receptor Ca2+-release channels on the sarcoplasmic reticulum to release additional Ca2+ into the cytoplasm.

What is the role of the ryanodine receptor in cardiac muscle?

The ryanodine receptor is the SR Ca2+-release channel activated during calcium-induced calcium release.

What is the role of SERCA in cardiac myocytes?

SERCA is the sarco(endo)plasmic reticulum Ca2+-ATPase that pumps cytosolic Ca2+ back into the sarcoplasmic reticulum.

What is the effective refractory period (ERP)?

The ERP is the period during which the cardiac cell is refractory to initiation of a new propagated action potential; no new propagated AP can be generated.

What is the relationship between Na+ channels and the ERP of fast-response fibers?

During the ERP, voltage-gated Na+ channels are inactivated and unavailable to initiate another propagated action potential.

What is the relative refractory period (RRP)?

During the RRP, a stronger-than-normal stimulus can generate a second, usually smaller action potential because Na+ channels are partially recovering from inactivation.

What determines the refractory period of slow-response fibers?

The refractory behavior of slow-response fibers is related to the status and recovery of Ca2+ channels rather than the fast Na+ channels that determine refractoriness in fast-response fibers.

How is ERP related to cardiac action potential duration?

ERP generally correlates with action potential duration; the long cardiac AP produces a correspondingly long effective refractory period.

Why is the long cardiac ERP physiologically important?

The long ERP prevents tetanization of cardiac muscle, allowing the heart to relax and refill between contractions.

Why is ERP clinically important?

ERP is an important determinant of the formation and termination of cardiac arrhythmias.

How does hyperkalemia change the cardiac resting membrane potential?

Hyperkalemia makes the resting membrane potential more positive, initially increasing excitability.

How does hyperkalemia affect voltage-gated Na+ channels and phase 0?

The more positive membrane potential slows Na+ channel recovery from inactivation, reducing the velocity of phase 0 depolarization and potentially widening the QRS.

How does severe hyperkalemia cause cardiac arrest?

If the membrane potential remains sufficiently depolarized, Na+ channels cannot adequately recover from inactivation, causing loss of excitability and potentially cardiac arrest.

How does hyperkalemia affect repolarization and AP duration?

Hyperkalemia increases K+ permeability by opening more K+ channels, accelerating repolarization and shortening action potential duration.

What ECG changes are associated with hyperkalemia in the lecture?

Increased or peaked T-wave amplitude and QRS widening can occur; severe hyperkalemia may progress to ventricular fibrillation or cardiac arrest.

How does hypokalemia affect the resting membrane potential and K+ permeability?

Hypokalemia moves the membrane potential to a more negative level and decreases K+ permeability because fewer K+ channels are open.

How does hypokalemia affect ventricular repolarization and AP duration?

Reduced K+ permeability delays repolarization, increases ventricular action potential duration, and prolongs the QT interval, increasing the risk of ventricular arrhythmias.

What ECG changes are associated with hypokalemia?

Hypokalemia is associated with flattened T waves, appearance of U waves, and QT prolongation.