The Relationship between Charge Movements Associated with ICa and INa-Ca in Cardiac Myocytes

Ventricular myocytes exhibit a nifedipine-sensitive inward calcium current (I_Ca) and contracture when they are voltage clamped from -40 to 0 millivolt in the presence of caffeine and in the absence of extracellular sodium. However, upon repolarization they fail to relax because neither the sarcoplasmic reticulum nor the sodium-calcium exchange can reduce intracellular calcium. Sudden application of extracellular sodium during the contracture (but after repolarization) causes immediate relaxation and activates a transient inward sodium-calcium exchange current (I_Na-Ca), whose peak slightly precedes mechanical relaxation. The total charge carried by the nifedipine-sensitive I_Ca is twice the total charge carried by the transient inward I_Na-Ca. Assuming an exchange stoichiometry of three sodium to one calcium, these results indicate that all the calcium entering the cell during the initial depolarization is extruded by the sodium-calcium exchange.