Snapshot A 60-year-old man presents to his cardiologist for a follow-up of newly diagnosed diastolic heart failure. He has a history of asthma and chronic obstructive lung disease. He reports that his pulmonologist does not want him to take β-blockers. However, his cardiologist wants to start him on a medication to slow the heart rate. He reassures the patient that this drug acts not on β-receptors but on a Ca2+ channel. (Verapamil) Introduction Ions responsible for the action potential of atria, ventricles, and Purkinje fibers are the same upstroke inward Na+ current plateau slow inward Ca2+ current via L-type voltage-gated Ca2+ channels a sustained period of depolarization allows for ventricular filling Ventricular Action Potential Resting membrane potential -85 mV resting membrane potential is maintained by inward rectifier K+ channels inward rectifier K+ channels open at rest and close with depolarization Phase 0, upstroke rapid depolarization caused by the opening of voltage-gated Na+ channels and inward Na+ current Na+ current depolarizes cell membrane, which closes inward rectifier K+ channels Phase 1, initial repolarization brief repolarization and net outward current inactivation gates on Na+ channels close Na+ current is decreased outward K+ current down an electrochemical gradient Phase 2, plateau stable, long period of depolarized membrane potential inward and outward current are equal, with no net current flow inward Ca2+ current (slow inward current) opened L-type Ca2+ channels blocked by Ca2+ channel blockers entry of Ca2+ also triggers the release of more Ca2+ from sarcoplasmic reticulum in the cell (Ca2+-induced Ca2+ release) outward K+ current driven by electrochemical driving force Phase 3, repolarization net outward current L-type voltage-gated Ca2+ channels close a decrease in inward Ca2+ current delayed rectifier K+ channels open completely and repolarize the membrane increase in outward K+ current inward rectifier K+ channels re-open Phase 4, resting membrane potential inward and outward currents are equal delayed rectifier K+ channels close inward rectifier K+ channels are fully open, resetting resting membrane potential at -85 mV