Postischemic Na+-K+-ATPase reactivation is delayed in the absence of glycolytic ATP in isolated rat hearts

Normalization of intracellular sodium (Na-i(+)) after postischemic reperfusion depends on reactivation of the sarcolemmal Na+-K+-ATPase. To evaluate the requirement of glycolytic ATP for Na+-K+-ATPase function during postischemic reperfusion, 5-s time-resolution Na-23 NMR was performed in isolated perfused rat hearts. During 20 min of ischemia, Na-i(+) increased approximately twofold. In glucose-reperfused hearts with or without prior preischemic glycogen depletion, Na-i(+) decreased immediately upon postischemic reperfusion. In glycogen-depleted pyruvate-reperfused hearts, however, the decrease of Na-i(+) was delayed by similar to 25 s, and application of the pyruvate dehydrogenase (PDH) activator dichloroacetate (DA) did not shorten this delay. After 30 min of reperfusion, Na-i(+) had almost normalized in all groups and contractile recovery was highest in the DA-treated hearts. In conclusion, some degree of functional coupling of glycolytic ATP and Na+-K+-ATPase activity exists, but glycolysis is not essential for recovery of Na-i(+) homeostasis and contractility after prolonged reperfusion. Furthermore, the delayed Na+-K+-ATPase reactivation observed in pyruvate-reperfused hearts is not due to inhibition of PDH.