Potassium channel openers depolarize hippocampal mitochondria

被引:88
作者
Debska, G
May, R
Kicinska, A
Szewczyk, A
Elger, CE
Kunz, WS
机构
[1] Univ Bonn, Med Ctr, Dept Epileptol, D-53105 Bonn, Germany
[2] M Nencki Inst Expt Biol, Lab Intracellular Ion Channels, PL-02093 Warsaw, Poland
关键词
hippocampus; mitochondria; potassium channel opener; glibenclamide; 5-hydroxydecanoic acid; mitochondrial ATP-regulated potassium channel;
D O I
10.1016/S0006-8993(00)03187-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We investigated the effect of the potassium channel openers diazoxide and RP66471 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. Concomitant with the depolarization was an increase of mitochondrial respiration. Furthermore, the mitochondrial membrane depolarization induced by diazoxide 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 channel openers diazoxide and RP66471 increased mitochondrial matrix volume and induced a release of cytochrome c from hippocampal mitochondria. These results indicate the presence of a mitochondrial ATP-regulated potassium channel in rat hippocampus being a target for potassium channel openers. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:42 / 50
页数:9
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