Glibenclamide inhibits mitochondrial K+ and Na+ uniports induced by magnesium depletion.
Magnesium depletion induces K+ and Na+ uniports in rat liver mitochondria. The purpose of the present study was to investigate the effects exerted by the antidiabetic sulfonylurea, glibenclamide, a well known blocker of ATP-sensitive potassium channels, on mitochondrial K+ and Na+ uniports. The K+ and Na+ uniport activities were monitored indirectly, in energized mitochondria, by following K+ and Na+ influxes as measured by light scattering. The membrane potential of the mitochondria was determined using a TPP+ selective electrode. Equilibrium binding measurements of glibenclamide to the inner mitochondrial membrane was performed with [3H]glibenclamide. Mitochondrial K+ and Na+ uniports were found to be inhibited by glibenclamide in a concentration-dependent manner, with IC50 of 20 +/- 7 and 15 +/- 8 microM, respectively. On lowering of the pH value, the potency of glibenclamide to inhibit the uniports activity was increased. Binding studies revealed the presence of a single class of low affinity binding sites for glibenclamide in the inner mitochondrial membrane, with a Kd of 4 +/- 2 microM and a BMAX of 148 +/- 50 pmoles/mg of protein. The present study provides evidence that both mitochondrial K+ and Na+ uniport activities are sensitive to the antidiabetic sulfonylurea, glibenclamide.
Szewczyk
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A
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Pikuła
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S
Wójcik
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G
Nałecz
M J
MJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D007004:Hypoglycemic Agents; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D005905:Glyburide