Cardiac Myocyte Action Potential Process
The cardiac action potential consists of five distinct phases (0-4) that involve coordinated ion channel activity, with sodium influx causing rapid depolarization, calcium influx maintaining the plateau phase, and potassium efflux driving repolarization, as described by the American College of Cardiology. 1
Phase 0: Rapid Depolarization
- Triggered by electrical stimulation reaching threshold potential (-70 to -90 mV)
- Voltage-gated sodium channels open rapidly
- Massive sodium influx (INa) into the cell occurs
- Membrane potential quickly rises from negative to positive (+20 to +30 mV)
- Characterized by steep upstroke with high velocity (dV/dt)
- This phase is critical for initiating cardiac contraction and propagating the electrical signal
Phase 1: Early Repolarization
- Rapid but brief partial repolarization
- Sodium channels inactivate quickly
- Transient outward potassium current (Ito) activates
- Potassium efflux creates the characteristic "notch" in ventricular action potentials
- More prominent in epicardial cells than endocardial cells
- Creates the "spike and dome" morphology in some cardiac regions 2
Phase 2: Plateau Phase
- Unique to cardiac myocytes (absent in neurons)
- L-type calcium channels open, allowing calcium influx (ICa-L)
- Calcium entry is balanced by potassium efflux (IKs, IKr)
- Membrane potential remains relatively stable near 0 mV
- Prolonged duration (200-400 ms) compared to neuronal action potentials
- Critical for:
Phase 3: Repolarization
- Progressive repolarization to resting potential
- Inactivation of calcium channels
- Continued activation of delayed rectifier potassium channels (IKr, IKs)
- Activation of inward rectifier potassium channels (IK1)
- Potassium efflux dominates, restoring negative membrane potential
- Establishes refractory period preventing premature excitation 1
Phase 4: Resting Phase
- Stable resting membrane potential (-80 to -90 mV)
- Maintained primarily by inward rectifier potassium channels (IK1)
- Na+/K+ ATPase pumps restore ion gradients (3 Na+ out, 2 K+ in)
- In pacemaker cells, spontaneous depolarization occurs due to:
Regional Differences in Action Potential
- Sinoatrial node: Less negative resting potential, spontaneous phase 4 depolarization, slower upstroke
- Atrial myocytes: Shorter action potential duration than ventricular cells
- Ventricular epicardium vs. endocardium: Different Ito expression creating transmural heterogeneity
- Purkinje fibers: Longer action potential duration, more prominent phase 1 notch 5
Subcellular Organization of Ion Channels
- Ion channels are not randomly distributed but organized in specific microdomains:
- T-tubules: Enriched in L-type calcium channels
- Intercalated discs: Sodium channels and gap junctions
- Caveolae/lipid rafts: Various ion channels and regulatory proteins
- This spatial organization ensures proper excitation-contraction coupling and intercellular conduction 6
Clinical Significance
- Alterations in ion channel function can lead to arrhythmias:
- Sodium channel dysfunction: Conduction disorders, Brugada syndrome
- Calcium channel abnormalities: Contractile dysfunction
- Potassium channel issues: Repolarization disorders (Long QT, Short QT)
- Many antiarrhythmic medications target specific ion channels to modify action potential properties 5, 7
Species Differences
- Important to note that rodent action potentials differ significantly from human:
- Shorter action potential duration
- More prominent transient outward current
- Different calcium handling
- Often lacking a clear plateau phase
- These differences must be considered when extrapolating experimental findings to human physiology 5