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Adenine Nucleotide Translocase Mediates the KATP-Channel-Openers-Induced Proton and Potassium Flux to the Mitochondrial Matrix

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Abstract

KATP channel openers have been shown to protect ischemic-reperfused myocardium by mimicking ischemic preconditioning, although their mechanisms of action have not been fully clarified. In this study we investigated the influence of the adenine nucleotide translocase (ANT) inhibitors–carboxyatractyloside (CAT) and bongkrekic acid (BA)–on the diazoxide- and pinacidil-induced uncoupling of isolated rat heart mitochondria respiring on pyruvate and malate (6 + 6 mM). We found that both CAT (1.3 μM) and BA (20 μM) markedly reduced the uncoupling of mitochondrial oxidative phosphorylation induced by the KATP channel openers. Thus, the uncoupling effect of diazoxide and pinacidil is evident only when ANT is not fixed by inhibitors in neither the C- nor the M-conformation. Moreover, the uncoupling effect of diazoxide and pinacidil was diminished in the presence of ADP or ATP, indicating a competition of KATP channel openers with adenine nucleotides. CAT also abolished K+-dependent mitochondrial respiratory changes. Thus ANT could also be involved in the regulation of KATP-channel-openers-induced K+ flux through the inner mitochondrial membrane.

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Authors and Affiliations

  1. Institute for Biomedical Research, Kaunas University of Medicine, Eiveniu Street 4, LT-3007, Kaunas, Lithuania

    Dalia M. Kopustinskiene & Adolfas Toleikis

  2. Department of Applied Chemistry and Microbiology, University of Helsinki, Viikki Biocenter 1, Helsinki, Finland

    Nils-Erik L. Saris

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  1. Dalia M. Kopustinskiene
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  2. Adolfas Toleikis
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  3. Nils-Erik L. Saris
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Correspondence to Dalia M. Kopustinskiene.

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Kopustinskiene, D.M., Toleikis, A. & Saris, NE.L. Adenine Nucleotide Translocase Mediates the KATP-Channel-Openers-Induced Proton and Potassium Flux to the Mitochondrial Matrix. J Bioenerg Biomembr 35, 141–148 (2003). https://doi.org/10.1023/A:1023746103401

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