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

Interuniversity Cardiology Institute of The Netherlands and Department of Cardiology, Heart Lung Institute, University Medical Center, 3508 GA Utrecht, The Netherlands Normalization of intracellular sodium (Na ) 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 23 Na NMR was performed in isolated perfused rat hearts. During 20 min of ischemia, Na increased approximately twofold. In glucose-reperfused hearts with or without prior preischemic glycogen depletion, Na decreased immediately upon postischemic reperfusion. In glycogen-depleted pyruvate-reperfused hearts, however, the decrease of Na was delayed by ~25 s, and application of the pyruvate dehydrogenase (PDH) activator dichloroacetate (DA) did not shorten this delay. After 30 min of reperfusion, Na 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 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. 23 Na NMR spectroscopy; oxidative phosphorylation; glycogen; compartmentalization