AJP - Heart and Circulatory Physiology, Vol 253, Issue 5 1026-H1034, Copyright © 1987 by American Physiological Society

ARTICLES

Sarcolemmal Na+-Ca2+ exchange activity in hearts subjected to hypoxia reoxygenation

I. M. Dixon, D. A. Eyolfson and N. S. Dhalla
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Winnipeg, Canada.

Although the occurrence of intracellular Ca2+ overload is known to be an important factor in hypoxia-reoxygenation injury, the exact mechanisms for this abnormality are not presently clear. Since Na+-Ca2+ exchange in the sarcolemmal membrane is considered to be involved in Ca2+ efflux, this study was undertaken to examine the effect of hypoxia reoxygenation on this system. Isolated rat hearts were made hypoxic by perfusing with a substrate-free medium gassed with 95% N2-5% CO2 and then reperfused with oxygenated normal medium. Hypoxia was found to markedly increase the resting tension and depress the ability of the heart to generate contractile force; reoxygenation resulted in partial recovery of these parameters. Sarcolemmal vesicles were isolated from control, hypoxic, and hypoxia-reoxygenated hearts, and the Na+-dependent Ca2+ uptake activity was measured at different times of incubation as well as at different concentrations of calcium. Sarcolemmal ATP-dependent Ca2+ accumulation was also measured for the purpose of comparison. A significant decrease in Na+-dependent Ca2+ uptake was observed in preparations from hearts made hypoxic for 10 min. Reoxygenation of 10-min hypoxic hearts resulted in a further depression of Na+-Ca2+ exchange activity. ATP-dependent Ca2+ accumulation was also depressed in hypoxic as well as reoxygenated hearts. These results suggest a defect in the Na+-Ca2+ exchange system and the ATP-dependent Ca2+ pump in the heart sarcolemmal membrane, and this may contribute to the occurrence of intracellular Ca2+ overload and functional abnormalities due to hypoxia-reoxygenation injury.

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