Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability

Journal of Biochemical and Molecular Toxicology
Maria A S FernandesJoaquim A F Vicente

Abstract

The interference of glibenclamide, an antidiabetic sulfonylurea, with mitochondrial bioenergetics was assessed on mitochondrial ion fluxes (H+, K+, and Cl-) by passive osmotic swelling of rat liver mitochondria in K-acetate, KNO3, and KCl media, by O2 consumption, and by mitochondrial transmembrane potential (Deltapsi). Glibenclamide did not permeabilize the inner mitochondrial membrane to H+, but induced permeabilization to Cl- by opening the inner mitochondrial anion channel (IMAC). Cl- influx induced by glibenclamide facilitates K+ entry into mitochondria, thus promoting a net Cl-/K+ cotransport, Deltapsi dissipation, and stimulation of state 4 respiration rate. It was concluded that glibenclamide interferes with mitochondrial bioenergetics of rat liver by permeabilizing the inner mitochondrial membrane to Cl- and promoting a net Cl-/K+ cotransport inside mitochondria, without significant changes on membrane permeabilization to H+.

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Citations

Apr 26, 2008·Journal of Cardiovascular Pharmacology·Matthias L RiessDavid F Stowe
May 17, 2005·British Journal of Pharmacology·Jolanta SkalskaAdam Szewczyk
Feb 3, 2011·Cell Biochemistry and Function·Sandonaid Andrei GeislerRoberto Barbosa Bazotte
Apr 25, 2013·Biochemical and Biophysical Research Communications·Viera KominkovaZuzana Tomaskova
Apr 15, 2014·Journal of the Neurological Sciences·Alice Vieira da CostaFoued Salmen Espindola
May 4, 2007·American Journal of Physiology. Cell Physiology·Roberto ScatenaBruno Giardina
Dec 1, 2017·PLoS Neglected Tropical Diseases·Julia A LoosAndrea C Cumino

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