Cardiac action potential

Cardiac muscle cells generate a much longer action potential than skeletal muscle or neurons, and that duration is what prevents the heart from tetanizing. Two distinct waveforms exist. Atrial and ventricular myocytes plus the His-Purkinje system produce a fast response; the sinoatrial and atrioventricular nodes produce a slow response with automaticity.

The ventricular myocyte action potential has five phases. Phase 0 is rapid depolarization driven by voltage-gated sodium channels opening. Phase 1 is a brief notch of initial repolarization as those sodium channels inactivate and a transient outward potassium current flows. Phase 2 is the plateau unique to cardiac tissue, in which calcium entering through L-type calcium channels roughly balances potassium leaving; that calcium triggers further calcium release from the sarcoplasmic reticulum and drives contraction. Phase 3 is rapid repolarization as calcium channels close and delayed rectifier potassium efflux dominates. Phase 4 is the resting membrane potential near −90 mV, held there by inward rectifier potassium conductance.

Nodal cells behave differently. They have no phases 1 or 2, their phase 0 upstroke is carried by slow L-type calcium channels rather than sodium channels, and their phase 4 is not flat. Instead a funny current carrying sodium inward produces slow spontaneous diastolic depolarization that drifts the cell to threshold on its own — the basis of automaticity. The slope of that phase 4 drift sets the heart rate, and it is the target of autonomic input: sympathetic stimulation steepens it and parasympathetic stimulation flattens it. Because the nodal upstroke depends on slow calcium channels, conduction through the AV node is slow, producing the delay that lets the ventricles fill before they contract.

During most of the action potential the cell cannot be re-excited. This refractory period, imposed largely by sodium channel inactivation, protects against premature reactivation and reentrant rhythms.

USMLE Step 1 draws heavily on these phases, most often by connecting them to pharmacology and pathology: sodium channel blockers acting on phase 0 of fast-response cells, potassium channel blockers prolonging phase 3 and the QT interval, and calcium channel blockers and beta blockers acting on nodal phase 0 and phase 4. Being able to name the dominant ion in each phase, and to distinguish fast from slow response tissue, answers most questions on the topic.