[CA2-DEPENDENT MEMBRANE CURRENTS IN GUINEA-PIG VENTRICULAR CELLS IN THE ABSENCE OF NA(](I))CA EXCHANGE/

Transient inward currents (I-ti) during oscillations of intracellular [Ca2+] ([Ca2+](i)) in ventricular myocytes have been ascribed to Na/Ca exchange. We have investigated whether other Ca2+-dependent membrane currents contribute to I-ti in single guinea-pig ventricular myocytes, by examining membrane currents during [Ca2+](i) oscillations and duri ng caffeine-induced Ca2+ release from the sarcoplasmic reticulum in th e absence of Na+. Membrane currents were recorded during whole-cell vo ltage clamp and [Ca2+](i) measured simultaneously with fura-2. In the absence of Na/Ca exchange, i.e., with Li+, Cs+ or N-methyl-D-glucamine (NMDG(+)) substituted for Na+, the cell could be loaded with Ca2+ by r epetitive depolarizations to +10 mV, resulting in spontaneous [Ca2+](i ) oscillations. During these oscillations, no inward currents were see n, but instead spontaneous Ca2+ release was accompanied by a shift of the membrane current in the outward direction at potentials between -4 0 mV and +60 mV. This [Ca2+](i)-dependent outward current shift was no t abolished when NMDG(+) was substituted for internal monovalent catio ns, nor was it sensitive to substitution of external Cl-. It was howev er, sensitive to the blockade of I-Ca by verapamil. These results sugg est that the transient outward current shift observed during spontaneo us Ca2+ release represents [Ca2+](i)-dependent transient inhibition of I-Ca. Similarly, during the [Ca2+](i) transients induced by brief caf feine (10 mM) applications, we could not detect membrane currents attr ibutable to a Ca2+-activated nonselective cation channel, or to a Ca2-activated Cl- channel; however, transient Ca2+-dependent inhibition o f I-Ca was again observed. We conclude that neither the Ca2+-activated nonselective cation channel nor the Ca2+-activated Cl- channel contri bute significantly to the membrane currents during spontaneous [Ca2+]( i) oscillations in guineapig ventricular myocytes. However, in the vol tage range between -40 mV and +60 mV Ca2+-dependent transient inhibiti on of I-Ca will contribute to the oscillations of the membrane current .