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.

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CARDIAC ACTION POTENTIAL

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Fast-Response Fibers

(Cardiac Muscle & His–Purkinje System)

Phase 0 – Rapid Depolarization

• Opening of Na⁺ channels
• Rapid sodium influx (fast I_Na) 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 (I_Ca-L)
• Balanced by outward K⁺ current (I_K)

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

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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

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Slow-Response Fibers

(SA Node & AV Node)

Phase 0 – Depolarization

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

Class IV antiarrhythmic drugs slow or block Phase 0

Phase 4 – Pacemaker Potential

• Inward Na⁺ current (I_f)
• Inward Ca²⁺ current (I_Ca-T)
• Outward K⁺ current (I_K)

Class II and Class IV antiarrhythmic drugs slow the Phase 4

 

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Activity

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Automaticity

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

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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

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Voltage-Gated Na⁺ Channels

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

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Autonomic Regulation of Heart Rate

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

Increased cAMP Causes:

• ↑ I_Ca-L → Faster upstroke
• ↑ I_K → Shorter AP duration
• ↑ I_f → ↑ Phase 4 slope
• ↑ Heart Rate

Decreased cAMP Causes:

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

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

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Activity