Protective effects of the potassium channel opener-diazoxide against injury in neonatal rat ventricular myocytes.
The mitochondrial ATP-regulated potassium channel is present in the inner membrane of heart mitochondria. Similarly to plasma membrane K(ATP), the mitochondrial channel is inhibited by antidiabetic sulfonylureas and activated by potassium channel openers, such as diazoxide. In the present work, the cytoprotective properties of diazoxide on the H9c2 cardiac myoblast cell line and neonatal rat ventricular cardiomyocytes were analysed. It was observed that 100 micromol/l diazoxide protected neonatal rat ventricular cardiomyocytes, but not H9c2 myoblasts, against injury induced by hydrogen peroxide or simulated ischemia. Moreover, diazoxide prevented hydrogen peroxide-induced mitochondrial potential depolarisation in neonatal rat ventricular cardiomyocytes. Diazoxide, at the same time, did not affect the expression level of the anti-apoptotic protein bcl-2 in these cells. The protective effects of diazoxide were suppressed by 5-hydroxydecanoic acid, a potassium channel blocker. These observations suggest that activation of the mitochondrial ATP-regulated potassium channel plays an important role in protection of neonatal cardiomyocytes against injury.
Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Warsaw, Poland.
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Szewczyk
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D002460:Cell Line; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000187:drug effects*; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052853:5-hydroxydecanoic acid; D006861:Hydrogen Peroxide; D003981:Diazoxide