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

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, KNO 3 , and KCl media, by O 2 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