Potassium channel openers depolarize hippocampal mitochondria

We investigated the effect of the potassium channel openers diazoxide and R P66471 on mitochondrial membrane potential and mitochondrial respiration in digitonin-treated rat hippocampal homogenates. Both diazoxide and RP66471 induced a dose-dependent decrease of mitochondrial membrane potential. Conc omitant with the depolarization was an increase of mitochondrial respiratio n. Furthermore, the mitochondrial membrane depolarization induced by diazox ide and RP66471 was significantly larger in the presence of potassium ions than in the presence of sodium ions. The diazoxide-induced (but not RP66471 -induced) mitochondrial membrane depolarization was partially inhibited by blockers of the ATP-regulated potassium channel, 5-hydroxydecanoic acid or the antidiabetic sulfonylurea glibenclamide. In addition, the potassium cha nnel openers diazoxide and RP66471 increased mitochondrial matrix volume an d induced a release of cytochrome c from hippocampal mitochondria. These re sults indicate the presence of a mitochondrial ATP-regulated potassium chan nel in rat hippocampus being a target for potassium channel openers. (C) 20 01 Elsevier Science B.V. All rights reserved.