Cardioprotective effects of KATP channel activation during hypoxia in goldfish Carassius auratus

The activation of ATP-sensitive potassium (K-ATP) ion channels in the heart is thought to exert a cardioprotective effect under low oxygen conditions, possibly enhancing tolerance of environmental hypoxia in aquatic vertebrates. The purpose of this study was to examine the possibility that hypoxia-induced activation of cardiac K-ATP channels, whether in the sarcolemma (sarcK(ATP)) or mitochondria (mitoK(ATP)), enhances viability in cardiac muscle cells from a species highly tolerant of low oxygen environments, the goldfish Carassius auratus. During moderate hypoxia (6-7 kPa), the activation of sarcK(ATP) channels was indicated by a reduction in transmembrane action potential duration (APD). This response to hypoxia was mimicked by the NO-donor SNAP (100 mu mol l(-1)) and the stable cGMP analog 8-Br-cGMP, but abolished by glibenclamide or L-NAME, an inhibitor of NO synthesis. The mitoK(ATP) channel opener diazoxide did not affect APD. Isolated ventricular muscle cells were then incubated under normoxic and hypoxic conditions. Cell viability was decreased in hypoxia; however, the negative effects of low oxygen were reduced during simultaneous exposure to SNAP, 8-Br-cGMP, and diazoxide. The cardioprotective effect of diazoxide, but not 8-Br-cGMP, was reduced by the mitoK(ATP) channel blocker 5-HD. These data suggest that hypoxia-induced activation of sarcK(ATP) or mitoK(ATP) channels could enhance tolerance of low-oxygen environments in this species, and that sarcK(ATP) activity is increased through a NO and cGMP-dependent pathway.