Defects in sarcolemmal Ca2+ transport in hearts due to induction of calcium paradox

Abstract

Na+-Ca2+ exchange and Ca2+-pump activities were studied in sarcolemmal vesicles isolated from rat hearts subjected to 'calcium paradox' on perfusion with Ca2+-free medium followed by reperfusion with medium containing 1.25 mM Ca2+. Perfusion of hearts with Ca2+-free medium for 5 minutes did not affect the Na+-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake, or Ca2+-stimulated ATPase activities in sarcolemma. Reperfusion of the Ca2+-deprived hearts with medium containing Ca2+ for 1-2 minutes increased Na+-dependent Ca2+ uptake, whereas reperfusion for 5-10 minutes decreased Na+-dependent Ca2+ uptake in sarcolemmal vesicles. Both ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities in sarcolemma were depressed on reperfusion of Ca2+-deprived hearts for 2-10 minutes. Reperfusion of Ca2+-deprived hearts for 5 minutes, which failed to generate contractile force, resulted in contracture without any recovery of the contractile force development. These changes in sarcolemmal Ca2+ transport and contractile function were prevented when hearts were perfused with Ca2+-free medium either in the presence of low sodium (35 nM) or at a low temperature (21°C) before starting the reperfusion. No alterations in the purity of the preparation or permeability of sarcolemmal vesicles with respect to Na+ or Ca2+ were detected in hearts perfused Ca2+-free medium or on reperfusion with medium containing calcium. The results indicate abnormalities in sarcolemmal Na+-Ca2+ exchange and Ca2+-pump mechanisms on reperfusion of Ca2+-deprived hearts with medium containing Ca2+, and such changes may partly account for the occurrence of intracellular Ca2+ overload during the development of calcium paradox.