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First published online July 6, 2005
Journal of Experimental Biology 208, 2765-2772 (2005)
Published by The Company of Biologists 2005
doi: 10.1242/jeb.01704
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Cardioprotective effects of KATP channel activation during hypoxia in goldfish Carassius auratus

Jerri Chen, Julia X. Zhu, Ingred Wilson and John S. Cameron*

Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA

* Author for correspondence (e-mail: jcameron{at}wellesley.edu)

Accepted 19 May 2005

The activation of ATP-sensitive potassium (KATP) 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 KATP channels, whether in the sarcolemma (sarcKATP) or mitochondria (mitoKATP), 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 sarcKATP channels was indicated by a reduction in transmembrane action potential duration (APD). This response to hypoxia was mimicked by the NO-donor SNAP (100 µmol l–1) and the stable cGMP analog 8-Br-cGMP, but abolished by glibenclamide or L-NAME, an inhibitor of NO synthesis. The mitoKATP 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 mitoKATP channel blocker 5-HD. These data suggest that hypoxia-induced activation of sarcKATP or mitoKATP channels could enhance tolerance of low-oxygen environments in this species, and that sarcKATP activity is increased through a NO and cGMP-dependent pathway.

Key words: hypoxia, ATP-sensitive K+ channels, KATP, nitric oxide, cardioprotection, goldfish, Carassius auratus




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