Introduction
The coordinated contraction of the heart relies on the precise electrical activity of ventricular myocytes, which are specialized contractile cardiomyocytes designed to generate force while maintaining rhythmicity. Unlike pacemaker cells, ventricular myocytes do not spontaneously depolarize; they rely on impulses from the conduction system (Purkinje fibers and gap junctions) to initiate action potentials.
The ventricular action potential (AP) is characterized by five distinct phases (0–4), each mediated by specific ion channels. These phases not only drive excitation–contraction coupling but also underlie the electrocardiogram (ECG), providing a clinical window into cardiac electrophysiology.
This article will provide a comprehensive overview of the ventricular action potential, including:
- Detailed explanation of phases 0–4
- Role of fast sodium channels, calcium plateau, and potassium currents
- Correlation with the ECG waveform
- Clinical relevance in arrhythmias, drug effects, and myocardial ischemia
1. Overview of Ventricular Action Potential
Ventricular myocytes exhibit a stable resting membrane potential (~−85 to −90 mV) maintained primarily by inward rectifier potassium channels (IK1). Upon receiving a depolarizing stimulus from neighboring cells via gap junctions, the ventricular membrane undergoes a rapid and sequential change in membrane potential, constituting the action potential.
Key Features
| Feature | Ventricular Myocyte |
|---|---|
| Resting potential | ~−85 mV |
| Excitable membrane | Na⁺-dependent depolarization |
| Duration | ~250–300 ms (human) |
| Plateau | Sustains contraction, prevents tetanus |
| Refractory period | Long, prevents premature re-excitation |
2. Phases of the Ventricular Action Potential
The ventricular AP is traditionally divided into five phases (0–4):
2.1 Phase 4 – Resting Membrane Potential
- Membrane Potential: ~−85 mV
- Ion Currents:
- IK1 (inward rectifier K⁺ channels): Maintain negative resting potential
- Small Na⁺ and Ca²⁺ leakage currents
- Function:
- Stabilizes the myocyte in a polarized state
- Prevents spontaneous depolarization (unlike SA node)
- Prepares the cell for rapid depolarization when stimulated
Clinical Relevance:
- Hyperkalemia reduces IK1 gradient → less negative resting potential → depolarization → arrhythmias
- Hypokalemia → hyperpolarization → delayed repolarization
2.2 Phase 0 – Rapid Depolarization
- Membrane Potential: Rapid upstroke from −85 mV toward +20 mV
- Dominant Ion Current: Fast Na⁺ influx (INa) via voltage-gated Na⁺ channels (Nav1.5)
- Mechanism:
- Depolarizing current from adjacent myocytes opens fast Na⁺ channels
- Rapid Na⁺ entry → steep upstroke of the action potential
Key Features:
| Property | Function |
|---|---|
| All-or-none | AP is triggered only if threshold (~−70 mV) is reached |
| Absolute refractory period begins | Prevents premature contraction |
| Conduction velocity | Determines speed of impulse through ventricular myocardium |
ECG Correlation: Phase 0 corresponds roughly to the QRS complex, reflecting ventricular depolarization.
Clinical Relevance:
- Sodium channel blockers (class I antiarrhythmics) slow Phase 0 → slower conduction, widened QRS
- Mutations in SCN5A gene → Brugada syndrome, conduction disorders
2.3 Phase 1 – Initial Repolarization
- Membrane Potential: Slight repolarization from peak (+20 mV) to ~+10 mV
- Ion Currents:
- Transient outward K⁺ current (Ito): Rapid K⁺ efflux
- Minor contribution from Cl⁻ efflux
- Function:
- Creates notch in the AP waveform
- Prepares membrane for plateau (Phase 2)
Clinical Relevance:
- Altered Ito can influence AP morphology → arrhythmogenic potential
- Predominantly studied in ventricular epicardium vs. endocardium
2.4 Phase 2 – Plateau Phase
- Membrane Potential: ~0 mV, relatively stable
- Ion Currents:
- L-type Ca²⁺ channels (ICa,L): Major inward current
- Delayed rectifier K⁺ channels (IKr, IKs): Outward currents balance inward Ca²⁺
- Mechanism:
- Inward Ca²⁺ entry prolongs depolarization
- Outward K⁺ currents prevent excessive depolarization
- Function:
- Sustains ventricular contraction
- Prevents premature re-excitation (long refractory period)
- Triggers excitation–contraction coupling via Ca²⁺-induced Ca²⁺ release from sarcoplasmic reticulum
Clinical Relevance:
- Drugs that block L-type Ca²⁺ channels → shorten plateau → reduced contractility (verapamil, diltiazem)
- Class III antiarrhythmics prolong plateau by K⁺ channel inhibition → prolong QT interval
ECG Correlation: Plateau corresponds roughly to the ST segment (ventricular depolarized state)
2.5 Phase 3 – Repolarization
- Membrane Potential: Returns from 0 mV to resting (~−85 mV)
- Ion Currents:
- Delayed rectifier K⁺ channels (IKr, IKs): Main outward K⁺ efflux
- Inward rectifier K⁺ (IK1): Restores resting potential
- Function:
- Ends ventricular contraction
- Sets duration of refractory period
- Restores ion gradients for next AP
ECG Correlation:
- Phase 3 repolarization corresponds to T wave on the ECG
Clinical Relevance:
- Prolonged repolarization → Long QT syndrome → risk of torsades de pointes
- Early afterdepolarizations (EADs) during Phase 3 can trigger arrhythmias
3. Ionic Basis of Each Phase – Detailed Summary
| Phase | Dominant Ion Channels | Ion Movement | Membrane Effect |
|---|---|---|---|
| Phase 4 | IK1 | K⁺ influx maintains resting potential | Stable, polarized |
| Phase 0 | INa (fast sodium) | Na⁺ influx | Rapid depolarization |
| Phase 1 | Ito | K⁺ efflux | Initial repolarization, AP notch |
| Phase 2 | ICa,L, IKr/IKs | Ca²⁺ influx, K⁺ efflux | Plateau, sustained contraction |
| Phase 3 | IKr, IKs, IK1 | K⁺ efflux | Repolarization to resting potential |
4. Excitation–Contraction Coupling
The ventricular AP is intimately linked to mechanical contraction:
- Phase 0–2: Ca²⁺ influx through L-type channels triggers Ca²⁺ release from sarcoplasmic reticulum (ryanodine receptors)
- Ca²⁺ binds to troponin C: Allows actin–myosin cross-bridge formation
- Phase 3: Ca²⁺ reuptake into SR via SERCA pump, cytoplasmic Ca²⁺ decreases → relaxation
The long plateau and refractory period prevent tetanic contractions, ensuring rhythmic pumping.
5. Refractory Periods
- Absolute refractory period: Covers Phase 0–early Phase 3 → no new AP can be generated
- Relative refractory period: Late Phase 3 → stronger-than-normal stimulus required
- Functional significance: Prevents arrhythmias and allows complete ventricular filling
6. Ventricular AP and ECG Correlation
| AP Phase | ECG Feature | Explanation |
|---|---|---|
| Phase 0 | QRS complex | Rapid ventricular depolarization |
| Phase 1–2 | ST segment | Plateau, ventricles fully depolarized |
| Phase 3 | T wave | Ventricular repolarization |
| Phase 4 | Baseline | Ventricular resting potential, ready for next beat |
Understanding this correlation is critical in diagnosing arrhythmias, ischemia, and electrolyte disturbances.
7. Pathophysiological Considerations
7.1 Ischemia
- Reduced ATP → impaired Na⁺/K⁺ ATPase → depolarized resting potential
- Reduced Ca²⁺ extrusion → cytosolic Ca²⁺ overload
- Shortened AP → ST segment changes on ECG
7.2 Electrolyte Imbalances
- Hyperkalemia: Less negative Phase 4 → slowed conduction, peaked T waves
- Hypokalemia: Prolonged repolarization → U waves, risk of arrhythmias
- Hypocalcemia: Prolonged Phase 2 → prolonged QT interval
7.3 Antiarrhythmic Drugs
| Class | Target | Effect on AP |
|---|---|---|
| I (Na⁺ blockers) | Phase 0 | Slow conduction, widen QRS |
| II (β-blockers) | Sympathetic modulation | Slow rate, decrease Ca²⁺ influx |
| III (K⁺ blockers) | Phase 3 repolarization | Prolong AP, QT interval |
| IV (Ca²⁺ blockers) | Phase 2/0 in nodal tissue | Reduce contractility, slow AV conduction |
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