SARCOLEMMAL CALCIUM TRANSPORTERS IN MYOCARDIAL-ISCHEMIA

To determine the potential pathophysiologic role of alterations in sar colemmal Ca2+ transport mechanisms, we investigated the effects of up to 120 min of global ischemia in the rabbit heart on the three major C a2+ transport proteins in the sarcolemma: the Na+-Ca2+ exchanger, the ATP-dependent Ca2+ pump, and the L-type Ca2+ channel, We purified sarc olemmal vesicles from control rabbit hearts and rabbit hearts made isc haemic for 20, 30, GO, 90, and 120 min. Purification of K+-p-nitrophen ylphosphatase activity was about 30-fold compared to the initial homog enate, and was the same for control and ischemic hearts. We measured t he initial velocity of Na+-Ca2+ exchange and found no inhibition after 20 min of ischemia, a 22% reduction in V-max after 30 min of ischemia , and approximately a 50% reduction in V-max after 60, 90, and 120 min of ischemia. At no time was there any change in the Ca2+ affinity of the Na+-Ca2+ exchanger. Solubilization and reconstitution of the Na+-C a2+ exchanger into asolectin vesicles restored the velocity to the sam e level as control reconstituted vesicles after 60 min of ischemia, bu t not after 90 or 120 min of ischemia. In contrast to Na+-Ca2+ exchang e, the initial velocity of the sarcolemmal ATP-dependent Ca2+ pump was unaffected by up to 2 h of ischemia. The number of L-type Ca2+ channe ls, measured by nitrendipine binding, was reduced by 21% after 60 min of ischemia. Decreased Ca2+ efflux due to direct inhibition of the Na-Ca2+ exchanger, as well as inhibition by low pH and increased intrace llular Na2+ in ischemia, probably contribute to Ca2+ overload and irre versible myocyte injury. Conversely, decreased Ca2+ influx due to decr eased availability of L-type Ca2+ channels, as well as decreased capac ity for reversed Na+-Ca2+ exchange, could contribute to contractile dy sfunction during ischemia and myocardial stunning following reperfusio n. (C) 1997 Academic Press Limited.