Learning Objective:

Explain the ionic basis and physiological significance of each phase of the ventricular, atrial, and Purkinje action potential, including the major ion channels involved, their relationship to ECG waves, and how antiarrhythmic drugs or inherited mutations alter these phases.

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Understanding the ionic mechanisms underlying cardiac action potentials is essential for clinical physiology, ECG interpretation, and the pharmacology of antiarrhythmic drugs. Many drugs act by binding to voltage-gated Na⁺, K⁺, or Ca²⁺ channels that generate these currents. This section focuses on the non-nodal action potentials of:

• Ventricular myocytes
• Atrial myocytes
• Purkinje fibers

Although there are small differences among these cell types, their overall patterns are similar. Because cardiac cells are connected by gap junctions, an action potential generated in one cell spreads rapidly to neighboring cells, ensuring coordinated activation.

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Phases of the Action Potential

Phase 0 – Rapid Upstroke

• Caused by the opening of fast voltage-gated Na⁺ channels
• Produces a steep depolarization
• High Na⁺ conductance drives the membrane potential toward ENa
• Conduction velocity is proportional to the slope of phase 0
  • β₁-adrenergic stimulation → ↑ slope → ↑ conduction velocity
• ECG correlate: QRS complex

Bridge to Pharmacology

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Phase 1 – Early Repolarization

• Small, brief repolarization
• Due to activation of transient outward K⁺ currents (Ito)
• Fast Na⁺ channels enter the inactivated state
• Contributes to shaping the early morphology of the AP

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Phase 2 – Plateau Phase

• Defining feature of cardiac muscle
• Due to a balance of inward and outward currents:
  • Ca²⁺ influx via L-type Ca²⁺ channels (ICa-L)
  • K⁺ efflux via delayed rectifier channels (e.g., IKr)
• Produces a nearly flat membrane potential

Physiological significance:

• Ca²⁺ entry triggers Ca²⁺-induced Ca²⁺ release from the SR → contraction
• Long duration prevents tetany
  • Ensures rhythmic pumping
• ECG correlate: ST segment

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Phase 3 – Repolarization

• L-type Ca²⁺ channels close
• K⁺ efflux increases via delayed rectifier K⁺ currents (IKr, IKs)
• IK₁ channels reopen late in phase 3, helping restore RMP
• ECG correlate: T wave

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Phase 4 – Resting Membrane Potential

• Stable resting potential (~ –85 to –90 mV)
• Maintained primarily by IK₁ (inward-rectifier K⁺ channels)
• Fast Na⁺ and L-type Ca²⁺ channels are closed
• Myocytes do not display automaticity

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Bridge to Pathology

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