M06.10.001 Cardiac action potential

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Learning Objective

By the end of this section, learners should be able to describe the phases of the cardiac action potential in fast- and slow-response fibers and correlate these phases with the mechanisms of action of antiarrhythmic drugs.

CARDIAC ACTION POTENTIAL

Fast-Response Fibers

(Cardiac Muscle & His–Purkinje System)

Phase 0 – Rapid Depolarization

  • Opening of Na+ channels
  • Rapid sodium influx (fast INa) causes membrane depolarization
    • The rate of depolarization depends on:
    • Number of Na+ channels open
    • Resting membrane potential

Class I antiarrhythmic drugs slow or block Phase 0

Phase 1 – Initial Repolarization

  • Na+ channels become inactivated
  • Transient outward K+ current
  • Inward Cl– current may contribute to “notch”

No significant antiarrhythmic drug effect in this phase

Phase 2 – Plateau Phase

  • Slow Ca2+ influx (ICa-L)
  • Balanced by outward K+ current (IK)

No significant antiarrhythmic drug effect in this phase

Phase 3 – Repolarization

  • Ca2+ channels inactivate
  • Delayed rectifier K+ current increases

Class III antiarrhythmic drugs slow Phase 3 repolarization

Phase 4 – Resting Membrane Potential

  • Maintained by Na+/K+-ATPase activity

Determinants of Conduction Velocity

Factor Effect on Conduction
↓ Phase 0 Depolarization (Vmax) ↓ Conduction Velocity
Less Negative Threshold Potential Slower Conduction
More Negative Resting Potential Faster Conduction

Slow-Response Fibers

(SA Node & AV Node)

Phase 0 – Depolarization

  • No significant Na+ current
  • Dependent on Ca2+ influx:
    • ICa-L
    • ICa-T

Class IV antiarrhythmic drugs slow or block Phase 0

Phase 4 – Pacemaker Potential

  • Inward Na+ current (If)
  • Inward Ca2+ current (ICa-T)
  • Outward K+ current (IK)

Class II and Class IV antiarrhythmic drugs slow the Phase 4

 

Activity

Automaticity

The ability of cardiac cells to depolarize spontaneously. The fastest Phase 4 slope determines the pacemaker of the heart (normally the SA node).

Refractory Periods

Type Characteristic
Effective Refractory Period (ERP) No response to any stimulus
Relative Refractory Period (RRP) A strong stimulus may trigger a response

K+ channel blockers prolong ERP

Voltage-Gated Na+ Channels

  • Resting (Ready)
  • Open (Active)
  • Inactivated (Refractory)

Autonomic Regulation of Heart Rate

Receptor Effect cAMP Level
β1 (Sympathetic) ↑ HR ↑ cAMP
M2 (Parasympathetic) ↓ HR ↓ cAMP

Increased cAMP Causes:

  • ↑ ICa-L → Faster upstroke
  • ↑ IK → Shorter AP duration
  • ↑ If → ↑ Phase 4 slope
  • ↑ Heart Rate

Decreased cAMP Causes:

  • Opposite effects
  • Activates K+ current (IK/ACh)
  • ↓ Diastolic Depolarization
  • ↓ Heart Rate

Beta blockers reduce heart rate by preventing cAMP formation, primarily affecting SA and AV nodal tissues.

Activity