SODIUM/CALCIUM EXCHANGE MODULATES INTRACELLULAR CALCIUM OVERLOAD DURING POSTHYPOXIC REOXYGENATION IN MAMMALIAN WORKING MYOCARDIUM - EVIDENCE FROM AEQUORIN-LOADED FERRET VENTRICULAR MUSCLES

We tested the hypothesis that the intracellular Ca2+ overload of ventricular myocardium during the period of posthypoxic reoxygenation is mediated by transsarcolemmal Ca2+ influx via Na+/Ca2+ exchange. In aequorin-loaded, ferret right ventricular papillary muscles, blockers of the sarcolemmal and the sarcoplasmic reticulum Ca2+ channels, slowed the Ca2+ transient, producing a convex ascent during membrane depolarization, followed by a concave descent during repolarization. The magnitude of the Ca-i(2+) transient was affected by changes in the membrane potential, Na-i(+), Na-0(+), and Ca-0(2+) and was blocked by Ni2+, or dichlorbenzamil. The calculated Na+/Ca2+ exchange current was in the reverse mode (Ca2+ influx) during the ascending phase of the Ca-i(2+) transient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the Ca:+ transient. During hypoxic superfusion, the Ca:+ transient was abbreviated, which was associated with a shorter action potential duration. In contrast, immediately after reoxygenation, the Ca:+ transient increased to a! level greater than that of the control, even though the action potential remained abbreviated. This is the first demonstration on a beat-to-beat basis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is augmented and transports a significant amount of Ca2+ into the ventricular myocardial cell. The activation of the exchanger at the time of reoxygenation appears to be mediated by Na-i(+) accumulation, which occurs during hypoxia.