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

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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 (Δψ). 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, Δψ 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+. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:162–169, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20022

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