Cardiac Action Potential: Pacemaker Cells vs Ventricular Myocytes

**1. Core Ionic Differences** Cardiac action potentials are broadly divided into two physiological classes: 1. **Slow-Response (Pacemaker) Action Potential**: Occurs in the Sinoatrial (SA) node and Atrioventricular (AV) node. Characterized by spontaneous Phase 4 depolarization (automaticity) and absence of a stable resting membrane potential. 2. **Fast-Response Action Potential**: Occurs in atrial myocytes, ventricular myocytes, and the Purkinje conduction system. Features a stable Phase 4 resting membrane potential (~-90 mV) and a prominent Phase 2 plateau. **2. Fast-Response Ventricular Muscle Action Potential (Phases 0–4)** * **Phase 0 (Rapid Upstroke)**: Triggered when excitation reaches threshold (~-70 mV). Massive, rapid influx of sodium ions via voltage-gated **fast \( \text{Na}^+ \) channels** (INa). Membrane potential overshoots to approximately +20 to +30 mV. * **Phase 1 (Early Partial Repolarization)**: Rapid closure of fast \( \text{Na}^+ \) channels and brief efflux of potassium ions through transient outward potassium channels (Ito). * **Phase 2 (Plateau Phase)**: Hallmark of ventricular electrophysiology (duration ~200–300 ms). Maintained by a precise balance between **influx of \( \text{Ca}^{2+} \)** through voltage-gated L-type calcium channels (ICa,L) and **efflux of \( \text{K}^+ \)** through delayed rectifier potassium channels (IKr, IKs). This calcium entry triggers Calcium-Induced Calcium Release (CICR) from the sarcoplasmic reticulum via Ryanodine receptors (RyR2). * **Phase 3 (Rapid Terminal Repolarization)**: Inactivation of L-type \( \text{Ca}^{2+} \) channels and dominant outward \( \text{K}^+ \) current via delayed rectifier channels, driving the membrane back toward -90 mV. * **Phase 4 (Resting State)**: Stable membrane potential (~-90 mV) maintained by the inward rectifier potassium current (IK1) and the \( \text{Na}^+-\text{K}^+ \) ATPase pump (3 \( \text{Na}^+ \) out for 2 \( \text{K}^+ \) in). **3. Pacemaker Action Potential (SA Node Automaticity)** * **Phase 4 (Pre-potential / Pacemaker Potential)**: Resting membrane potential is unstable (-60 mV). Driven by: 1. *Funny Current (If)*: Inward mixed \( \text{Na}^+ \) current activated by hyperpolarization through HCN channels. 2. *T-type Calcium Current (ICa,T)*: Transient inward \( \text{Ca}^{2+} \) current assisting late Phase 4 depolarization up to the threshold of -40 mV. * **Phase 0 (Slow Depolarizing Upstroke)**: Phase 0 in nodal tissue is mediated entirely by inward **L-type calcium channels (ICa,L)**, NOT fast sodium channels. This accounts for the markedly slower conduction velocity (0.05 m/s in AV node vs 2–4 m/s in Purkinje fibers). * **Phase 3 (Repolarization)**: Inactivation of L-type calcium channels and activation of outward potassium currents (IK). **4. 🔬 High-Yield Clinical Correlations** * **Class I Antiarrhythmics (Lidocaine, Flecainide)**: Block fast sodium channels, selectively suppressing Phase 0 of ventricular and Purkinje fibers without suppressing the SA node upstroke. * **Class IV Antiarrhythmics (Verapamil, Diltiazem)**: Block L-type calcium channels, suppressing Phase 0 in the SA and AV nodes, effectively slowing heart rate and terminating AV nodal re-entrant tachycardias (AVNRT). * **Adenosine & Beta-Blockers**: Adenosine stimulates A1 receptors to activate potassium channels and suppress cAMP, hyperpolarizing nodal cells and transiently halting AV nodal conduction. **5. 📖 Standard Textbook Reference** * *Guyton and Hall Textbook of Medical Physiology*, 14th Ed., Unit III: The Heart, Ch. 9 & 10, pp. 103–126. * *Ganong's Review of Medical Physiology*, 26th Ed., Section IV: Cardiovascular Physiology, Ch. 29, pp. 521–538.