Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability
✍ Scribed by Maria A. S. Fernandes; Maria S. Santos; António J. M. Moreno; Gunars Duburs; Catarina R. Oliveira; Joaquim A. F. Vicente
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 123 KB
- Volume
- 18
- Category
- Article
- ISSN
- 1095-6670
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✦ Synopsis
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, 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