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 ventr icular myocardium during the period of posthypoxic reoxygenation is me diated by transsarcolemmal Ca2+ influx via Na+/Ca2+ exchange. In aequo rin-loaded, ferret right ventricular papillary muscles, blockers of th e sarcolemmal and the sarcoplasmic reticulum Ca2+ channels, slowed the Ca2+ transient, producing a convex ascent during membrane depolarizat ion, followed by a concave descent during repolarization. The magnitud e of the Ca-i(2+) transient was affected by changes in the membrane po tential, Na-i(+), Na-0(+), and Ca-0(2+) and was blocked by Ni2+, or di chlorbenzamil. The calculated Na+/Ca2+ exchange current was in the rev erse mode (Ca2+ influx) during the ascending phase of the Ca-i(2+) tra nsient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the Ca:+ transient. Durin g hypoxic superfusion, the Ca:+ transient was abbreviated, which was a ssociated with a shorter action potential duration. In contrast, immed iately after reoxygenation, the Ca:+ transient increased to a! level g reater than that of the control, even though the action potential rema ined abbreviated. This is the first demonstration on a beat-to-beat ba sis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is a ugmented and transports a significant amount of Ca2+ into the ventricu lar myocardial cell. The activation of the exchanger at the time of re oxygenation appears to be mediated by Na-i(+) accumulation, which occu rs during hypoxia.