action potential

Resting membrane potential (~-70 mV in neurons, ~-90 mV in cardiac ventricular myocytes) is maintained mainly by K+ leak channels and the Na+/K+ ATPase. When a stimulus depolarizes the membrane to threshold (~-55 mV in neurons), voltage-gated Na+ channels open rapidly, causing a fast upstroke (Phase 0) due to Na+ influx. Repolarization occurs as Na+ channels inactivate and voltage-gated K+ channels open, allowing K+ efflux (Phase 3), returning the membrane to resting potential, often with a brief hyperpolarization (undershoot) due to persistent K+ efflux. Neuronal APs follow the all-or-none principle and propagate via local depolarization currents; myelination increases conduction velocity via saltatory conduction at nodes of Ranvier. Refractory periods (absolute and relative) result from Na+ channel inactivation states, preventing the AP from immediately reversing direction, ensuring unidirectional propagation.

Cardiac APs, especially in ventricular myocytes, have additional phases: Phase 0 (rapid Na+ influx), Phase 1 (transient outward K+ current, notch), Phase 2 (plateau, Ca2+ influx through L-type channels balanced by K+ efflux), and Phase 3 (repolarization, K+ efflux dominates). The plateau phase is critical for excitation-contraction coupling (calcium-induced calcium release from the sarcoplasmic reticulum via ryanodine receptors) and prevents tetany by prolonging the refractory period. Pacemaker cells (SA/AV node) have a distinct AP lacking a true resting potential; they exhibit spontaneous Phase 4 depolarization due to funny current (If, Na+ influx) and have Phase 0 mediated by L-type Ca2+ channels rather than fast Na+ channels, with no Phase 1 or true plateau. Clinically important because antiarrhythmic drugs and local anesthetics target specific channels involved in AP phases (e.g., Class I antiarrhythmics block Na+ channels, Class III block K+ channels affecting repolarization). Skeletal muscle APs resemble neuronal APs but trigger a distinct excitation-contraction coupling via T-tubules and dihydropyridine receptors directly coupled to ryanodine receptors (mechanical coupling), unlike cardiac muscle's calcium-induced calcium release.