ATP-regulated potassium channel blocker, glibenclamide, uncouples mitochondria.
The purpose of the present study was to investigate the effect exerted by the antidiabetic sulfonylurea, glibenclamide, a well known blocker of ATP-regulated potassium channels, on membrane potential and proton gradient in rat liver mitochondria. Membrane potential of mitochondria was determined using a TPP+ selective electrode. Mitochondrial proton gradient value was measured with 2',7',bis(carboxyethyl)-5,6-carboxyfluorescein, the pH-sensitive fluorescent probe. Mitochondrial membrane potential and proton gradient were found to be dissipated by glibenclamide in a concentration-dependent manner, with IC50 of 70 +/- 7 microM. The present results provide evidence that the antidiabetic sulfonylurea, glibenclamide, uncouples rat liver mitochondria.
Szewczyk
A
A
Department of Muscle Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland.
Czyz
A
A
Nałecz
M J
MJ
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005905:Glyburide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005452:Fluoresceins; D005456:Fluorescent Dyes; D015221:Potassium Channels; D011506:Proteins; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D000255:Adenosine Triphosphate; D005905:Glyburide