Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

Y Kihara; S Sasayama; M Inoko; J P Morgan

doi:10.1172/JCI117082

Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

Y Kihara, S Sasayama, M Inoko, and J P Morgan

Published March 1, 1994 - More info

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Abstract

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 Cai2+ transient, producing a convex ascent during membrane depolarization, followed by a concave descent during repolarization. The magnitude of the Cai2+ transient was affected by changes in the membrane potential, Nai+, Nao+, and Cao2+, 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 Cai2+ transient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the Cai2+ transient. During hypoxic superfusion, the Cai2+ transient was abbreviated, which was associated with a shorter action potential duration. In contrast, immediately after reoxygenation, the Cai2+ 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 Nai+ accumulation, which occurs during hypoxia.