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Bongkrekic acid and atractyloside inhibits chloride channels from mitochondrial membranes of rat heart
Authors:Lubica Malekova  Miroslav Ferko  Olga Krizanova  Adam Szewczyk
Institution:a Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava, Slovak Republic
b Institute for Heart Research, Slovak Academy of Sciences, 83334 Bratislava, Slovakia
c Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland
Abstract:The aim of this work was to characterize the effect of bongkrekic acid (BKA), atractyloside (ATR) and carboxyatractyloside (CAT) on single channel properties of chloride channels from mitochondria. Mitochondrial membranes isolated from a rat heart muscle were incorporated into a bilayer lipid membrane (BLM) and single chloride channel currents were measured in 250/50 mM KCl cis/trans solutions. BKA (1-100 μM), ATR and CAT (5-100 μM) inhibited the chloride channels in dose-dependent manner. The inhibitory effect of the BKA, ATR and CAT was pronounced from the trans side of a BLM and it increased with time and at negative voltages (trans-cis). These compounds did not influence the single channel amplitude, but decreased open dwell time of channels. The inhibitory effect of BKA, ATR and CAT on the mitochondrial chloride channel may help to explain some of their cellular and/or subcellular effects.
Keywords:BLM  bilayer lipid membrane  Popen  open probability of single channel  Erev  reversal potential  SMP  submitochondrial particles  BKA  bongkrekic acid  ATR  atractyloside  CAT  carboxyatractyloside  CsA  cyclosporine A  MA  myristic acid  TBT  tributyltin  MPTP  mitochondrial permeability transition pore  IMAC  inner membrane anion channel
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