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The effect of atp-dependent potassium uptake on mitochondrial functions under acute hypoxia

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Abstract

The opening of mitochondrial K+ АТР-channel (mtK+ АТР-channel) is supposed to be important in the modulation of mitochondrial functions under hypoxia, but the underlying mechanisms have not been clarified yet. The aim of this work was to study the effect of acute hypoxia on mtK+ АТР-channel activity and to estimate the contribution of the channel in the modulation of mitochondrial functions. MtK+ АТР-channel activity was assessed polarographically from the rate of State 4 respiration and by potentiometric monitoring of potassium efflux from deenergized mitochondria. It was shown that hypoxia reliably increased mtK+ АТР-channel activity, which resulted in the changes of respiration rates (increase of State 4 and suppression of State 3 respiration), uncoupling (the decrease of respiratory control ratio) and suppression of phosphorylation. These effects were well mimicked by mtK+ АТР-channel opener diazoxide (DZ) in isolated rat liver mitochondria. MtK+ АТР-channel opening in vitro suppressed phosphorylation too, but increased phosphorylation efficiency, while mtK+ АТР-channel blockers reduced it dramatically. The correlation was established between mtK+ АТР-channel activity and the endurance of the rats to physical training under hypoxia. Hypoxia improved physical endurance, but treatment by mtK+ АТР-channel blockers glibenklamide and 5-hydroxydecanoate (5-HD) prior to hypoxia strongly reduced both the channel activity and the endurance limits. This was in accord with the observation that under glibenklamide and 5-HD administration hypoxia failed to restore mtK+ АТР-channel activity. Based on the experiments, we came to the conclusion that mtK+ АТР-channel opening played a decisive role in the regulation of energy metabolism under acute hypoxia via the modulation of phosphorylation system in mitochondria.

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Acknowledgments

The authors are indebted to Prof. Dr. Galina Mironova for generous permission to use K+-selective microelectrode.

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Authors and Affiliations

  1. Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Bogomoletz str. 4, 01601, Kiev, Ukraine

    Olga Akopova, Liudmila Kolchinskaya & Vadim Sagach

  2. Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine

    Valentina Nosar, Bronislav Gavenauskas, Larissa Bratus & Iryna Mankovska

Authors
  1. Olga Akopova
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  2. Valentina Nosar
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  3. Bronislav Gavenauskas
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  4. Larissa Bratus
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  5. Liudmila Kolchinskaya
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  6. Iryna Mankovska
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  7. Vadim Sagach
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Correspondence to Olga Akopova.

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Akopova, O., Nosar, V., Gavenauskas, B. et al. The effect of atp-dependent potassium uptake on mitochondrial functions under acute hypoxia. J Bioenerg Biomembr 48, 67–75 (2016). https://doi.org/10.1007/s10863-015-9642-8

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  • DOI: https://doi.org/10.1007/s10863-015-9642-8

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