Electrophysiologic experiments in cardiac tissue suggest that Ca2+ is involved in generation of the action potential, the pacemaker potential, and conduction of the slow wave of depolarization. For instance, removal of Ca2+ inhibits the slow inward current and prolongs the action potential and suppresses the slow diastolic depolarization. Divalant cations Mn2+, Co2+, Cd2+, Mg2+, block the slow inward current and suppress pacemaker activity, but shorten the action potential. Ni2+ specifically blocks the slow inward current and prolongs the action potential. Ca2+ also plays a central role in generation of diastolic depolarizaittn. Cd2+ inhibits the diastolic depolarizaton and the upstoke of the action potential in SA nodal cells, while blocking the time-dependent inward current in the pacemaker potential range and the time-dependent outward current. A variety of molecular transport systems ranging from the Ca-channel to a Ca2+-Na+ or Ca2+-K+ exchanges to Ca2+-induced activation of the K+ current have been postulated to explain the effects of Ca2+ on cardiac electrophysiologic processes.