The human heart is an extraordinary organ, capable of rhythmic contraction that sustains blood flow throughout the body. The action potential (AP) of cardiac muscle is central to this function, serving as the electrical trigger for coordinated contraction. Unlike skeletal muscle, cardiac action potentials are long-lasting, exhibit automaticity in pacemaker cells, and involve unique ion channel dynamics.
Understanding cardiac action potentials is fundamental for medical students, cardiologists, and researchers, as arrhythmias, conduction abnormalities, and heart failure are directly linked to alterations in cardiac electrical activity.
1. Introduction
Cardiac action potentials are transient changes in the transmembrane potential of cardiac cells caused by ion fluxes across the sarcolemma. They initiate excitation-contraction coupling, leading to mechanical contraction of the heart.
Two major types of cardiac muscle cells generate action potentials:
- Pacemaker cells (autorhythmic cells)
- Located in the sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje fibers
- Exhibit spontaneous depolarization (automaticity)
- Initiate the heart rhythm
- Contractile myocytes
- Comprise most of atrial and ventricular myocardium
- Exhibit long-duration action potentials with a plateau phase
- Respond to pacemaker signals to produce coordinated contraction
2. Resting Membrane Potential
The resting membrane potential (RMP) is the electrical potential across the cardiac cell membrane at rest. It is established primarily by:
- K⁺ permeability through inward rectifier channels (IK1)
- Na⁺/K⁺ ATPase pump maintaining ionic gradients
Typical resting membrane potentials:
- Ventricular and atrial myocytes: ~ -85 to -90 mV
- Pacemaker cells (SA node): ~ -60 mV (less negative, allowing spontaneous depolarization)
RMP is critical for excitability and determines the threshold for action potential initiation.
3. Ionic Basis of Cardiac Action Potentials
The cardiac action potential results from sequential opening and closing of voltage-gated ion channels, allowing ions to move across the membrane. The major ions involved include:
- Sodium (Na⁺): Rapid depolarization
- Calcium (Ca²⁺): Plateau phase and contraction
- Potassium (K⁺): Repolarization
- Chloride (Cl⁻): Minor role in shaping AP
4. Types of Cardiac Action Potentials
4.1 Pacemaker Action Potentials (SA/AV Node)
Pacemaker cells exhibit spontaneous depolarization, which triggers heart rhythm. The phases are:
Phase 4 – Pacemaker Potential (Spontaneous Depolarization)
- Gradual depolarization due to:
- If current (“funny” current): Mixed Na⁺/K⁺ inward current
- T-type Ca²⁺ channels: Contribute to late depolarization
- Determines heart rate
Phase 0 – Depolarization
- Slow depolarization due to L-type Ca²⁺ channels opening
- No fast Na⁺ channels are involved
- Initiates conduction to surrounding contractile cells
Phase 3 – Repolarization
- K⁺ efflux through delayed rectifier K⁺ channels (IK)
- Membrane potential returns to ~ -60 mV
4.2 Contractile Myocyte Action Potentials
Ventricular and atrial myocytes exhibit a long-duration action potential (~200–400 ms) to prevent tetany and ensure coordinated contraction. Phases include:
Phase 0 – Rapid Depolarization
- Triggered by Na⁺ influx via fast voltage-gated Na⁺ channels
- Membrane potential rises from ~ -85 mV to +20 mV
Phase 1 – Initial Repolarization
- Transient K⁺ efflux (Ito current)
- Brief notch in membrane potential
Phase 2 – Plateau Phase
- Balanced Ca²⁺ influx (L-type channels) and K⁺ efflux
- Maintains depolarization (~0 mV)
- Ensures sustained contraction and adequate ventricular ejection
Phase 3 – Rapid Repolarization
- K⁺ efflux predominates (IKr, IKs)
- Membrane potential returns to RMP
Phase 4 – Resting Potential
- Membrane potential maintained at ~ -85 to -90 mV
- Na⁺/K⁺ ATPase restores ionic gradients
5. Differences Between Pacemaker and Contractile APs
| Feature | Pacemaker AP | Contractile AP |
|---|---|---|
| Resting potential | -60 mV | -85 to -90 mV |
| Phase 0 | Slow, Ca²⁺ mediated | Fast, Na⁺ mediated |
| Plateau | Minimal | Prominent, Ca²⁺ influx |
| Duration | 150–200 ms | 200–400 ms |
| Automaticity | Yes | No (requires stimulus) |
| Refractory period | Short | Long (prevents tetany) |
6. Excitation-Contraction Coupling
Action potentials lead to cardiac muscle contraction via excitation-contraction coupling:
- AP propagates along sarcolemma and T-tubules
- L-type Ca²⁺ channels in T-tubules open during phase 2
- Ca²⁺ influx triggers ryanodine receptors on sarcoplasmic reticulum (SR) → calcium-induced calcium release (CICR)
- Intracellular Ca²⁺ binds troponin C, allowing actin-myosin cross-bridge cycling
- Contraction occurs during plateau phase
- Relaxation: Ca²⁺ reuptake into SR and extrusion via Na⁺/Ca²⁺ exchanger
7. Refractory Periods
Long-duration action potentials create absolute and relative refractory periods, preventing premature re-excitation:
- Absolute refractory period (ARP): No AP can be initiated
- Relative refractory period (RRP): Strong stimulus required
- Effective refractory period (ERP): Prevents tetany and ensures rhythmic contraction
8. Conduction System and AP Propagation
8.1 Sinoatrial (SA) Node
- Primary pacemaker, initiates AP
- Spontaneous depolarization sets heart rate (~60–100 bpm)
8.2 Atrioventricular (AV) Node
- Delays conduction (~0.1 sec) to allow atrial emptying
- AP propagation is slow due to small cell size and fewer gap junctions
8.3 His-Purkinje System
- Rapid conduction to ventricles
- Ensures synchronized ventricular contraction
8.4 Gap Junctions
- Allow electrical coupling between myocytes
- Essential for coordinated propagation of AP
9. Electrocardiogram (ECG) Correlation
Cardiac APs are reflected in the surface ECG:
- P wave: Atrial depolarization
- PR interval: AV nodal delay
- QRS complex: Ventricular depolarization (phase 0)
- ST segment: Plateau phase of ventricular AP
- T wave: Ventricular repolarization (phase 3)
ECG analysis allows detection of arrhythmias, conduction defects, and ischemia.
10. Modulation of Cardiac Action Potentials
10.1 Autonomic Nervous System
- Sympathetic stimulation:
- Increases slope of phase 4 depolarization in SA node
- Increases heart rate (positive chronotropy)
- Increases contractility (positive inotropy via enhanced Ca²⁺ influx)
- Parasympathetic stimulation (vagus nerve):
- Decreases slope of phase 4 depolarization
- Reduces heart rate (negative chronotropy)
- Slightly reduces atrial contractility
10.2 Pharmacological Modulation
- Beta-blockers: Reduce sympathetic effect on AP and contractility
- Calcium channel blockers: Reduce L-type Ca²⁺ influx → slower conduction and shorter plateau
- Antiarrhythmics: Modify ion channel currents to alter AP duration and refractory periods
11. Abnormalities of Cardiac Action Potentials
11.1 Early Afterdepolarizations (EADs)
- Occur during phase 2 or 3
- Can trigger torsades de pointes or ventricular tachycardia
11.2 Delayed Afterdepolarizations (DADs)
- Occur after repolarization
- Often caused by Ca²⁺ overload
- Can initiate ectopic beats
11.3 Conduction Blocks
- Failure of AP propagation through SA, AV, or Purkinje system
- Results in bradyarrhythmias or heart block
11.4 Long QT Syndrome
- Prolonged repolarization (phase 3)
- Increased risk of ventricular arrhythmias
12. Clinical Relevance
Understanding cardiac action potentials is crucial for:
- Arrhythmia diagnosis and treatment
- Drug development targeting ion channels
- Pacemaker design
- Understanding heart failure pathophysiology
- Interpreting ECG abnormalities in ischemia, infarction, and electrolyte disturbances
13. Advanced Concepts
13.1 Phase 2 and Calcium Handling
- Plateau phase is critical for excitation-contraction coupling
- Abnormal Ca²⁺ handling contributes to heart failure, hypertrophy, and arrhythmias
13.2 Pacemaker Automaticity
- “Funny current” (If) in SA node is a target for heart rate-controlling drugs like ivabradine
- Modulation of phase 4 slope adjusts cardiac rhythm
13.3 Regional Heterogeneity
- Atrial, ventricular, Purkinje, and nodal cells have distinct AP shapes
- Important in repolarization dispersion and arrhythmogenesis
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