Potassium channel openers depolarize hippocampal mitochondria.
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.
Debska
G
G
Laboratory of the Intracellular Ion Channels, Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland.
May
R
R
Kicińska
A
A
Szewczyk
A
A
Elger
C E
CE
Kunz
W S
WS
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001565:Benzoates / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000032:analysis; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D006880:Hydroxy Acids / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014634:Valinomycin / Q000494:pharmacology
D001565:Benzoates; D003574:Cytochrome c Group; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008051:Lipid Bilayers; D015221:Potassium Channels; D011725:Pyridines; C091972:RP 66471; D014634:Valinomycin; C052853:5-hydroxydecanoic acid; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide