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Closure of mitochondrial potassium channels favors opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria

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Abstract

It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca2+ activated (mitoKCa) potassium channels triggers opening of the mitochondrial permeability transition pore (MPTP) in cells and isolated mitochondria. We found earlier that the Tl+-induced MPTP opening in Ca2+-loaded rat liver mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled respiration and increase of mitochondrial swelling and ΔΨmito dissipation in the medium containing TlNO3 and KNO3. On the other hand, our study showed that the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl+-induced MPTP opening in the inner membrane of Ca2+-loaded rat heart mitochondria (Korotkov et al. 2013). Here we showed that 5-hydroxydecanoate increased the Tl+-induced MPTP opening in the membrane of rat liver mitochondria regardless of the presence of mitoKATP modulators (diazoxide and pinacidil). This manifested in more pronounced decrease in the uncoupled respiration and acceleration of both the swelling and the ΔΨmito dissipation in isolated rat liver mitochondria, incubated in the medium containing TlNO3, KNO3, and Ca2+. A slight delay in Ca2+-induced swelling of the mitochondria exposed to diazoxide could be result of an inhibition of succinate oxidation by the mitoKATP modulator. Mitochondrial calcium retention capacity (CRC) was markedly decreased in the presence of the mitoKATP inhibitor (5-hydroxydecanoate) or the mitoKCa inhibitor (paxilline). We suggest that the closure of mitoKATP or mitoKCa in calcium loaded mitochondria favors opening of the Tl+-induced MPTP in the inner mitochondrial membrane.

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Acknowledgments

We are thankful to Dr. Arshad Jahangir (Center for Integrative Research on Cardiovascular Aging, Aurora Research Institute, Aurora Health Care, US) for making suggestions for the manuscript improvements. Purchase of Dia, Pin, and 5-HD was financed by a grant from the Russian Foundation for Basic Research to Margarita V. Savina (N08-04- 00564a).

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No conflicts of interest, financial or otherwise, are declared by the authors.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia

    Sergey M. Korotkov, Irina V. Brailovskaya, Anton R. Shumakov & Larisa V. Emelyanova

  2. Center for Integrative Research on Cardiovascular Aging, Aurora Research Institute, Aurora Health Care, Milwaukee, WI, USA

    Larisa V. Emelyanova

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  1. Sergey M. Korotkov
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  2. Irina V. Brailovskaya
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  3. Anton R. Shumakov
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  4. Larisa V. Emelyanova
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Correspondence to Sergey M. Korotkov.

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Korotkov, S.M., Brailovskaya, I.V., Shumakov, A.R. et al. Closure of mitochondrial potassium channels favors opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria. J Bioenerg Biomembr 47, 243–254 (2015). https://doi.org/10.1007/s10863-015-9611-2

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