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