MECHANISM OF HYPOXIC K LOSS IN RABBIT VENTRICLE

Although a critical factor causing lethal ischemic ventricular arrhyth mias, net cellular K loss during myocardial ischemia and hypoxia is po orly understood, We investigated whether selective activation of ATP-s ensitive K (K-ATP) channels causes net cellular K loss by examining th e effects of the K-ATP channel agonist cromakalim on unidirectional K efflux, total tissue K content, and action potential duration (APD) in isolated arterially perfused rabbit interventricular septa, Despite i ncreasing unidirectional K efflux and shortening APD to a comparable d egree as hypoxia, cromakalim failed to induce net tissue K loss, rulin g out activation of K-ATP channels as the primary cause of hypoxic K l oss, Next, we evaluated a novel hypothesis about the mechanism of hypo xic K loss, namely that net K loss is a passive reflection of intracel lular Na gain during hypoxia or ischemia. When the major pathways prom oting Na influx were inhibited, net K loss during hypoxia was almost c ompletely eliminated, These findings show that altered Na fluxes are t he primary cause of net K loss during hypoxia, and presumably also in ischemia. Given its previously defined role during hypoxia and ischemi a in promoting intracellular Ca overload and reperfusion injury, this newly defined role of intracellular Na accumulation as a primary cause of cellular K loss identifies it as a central pathogenetic factor in these settings.