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Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability
Author(s) -
Fernandes Maria A. S.,
Santos Maria S.,
Moreno António J. M.,
Duburs Gunars,
Oliveira Catarina R.,
Vicente Joaquim A. F.
Publication year - 2004
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20022
Subject(s) - glibenclamide , bioenergetics , mitochondrion , membrane potential , biophysics , inner mitochondrial membrane , chemistry , microbiology and biotechnology , cotransporter , biochemistry , biology , endocrinology , organic chemistry , diabetes mellitus , sodium
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