Ukr.Biochem.J. 2011; Volume 83, Issue 3, May-Jun, pp. 37-47

The influence of ATP-dependent K(+)-channel diazoxide opener on the opening of mitochondrial permeability transition pore in rat liver mitochondria

O. V. Akopova

Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;

The influence of mitochondrial ATP-dependent­ K+-channel (K+АТР-channel) opener, diazoxide (DZ) on the mitochondrial permeabili­ty transition pore (MPTP) opening in rat liver mitochondria is studied. In the absence of DZ the MPTP opening leads to the increase in the rate of K+– and Ca2+-cycling supported by the simultaneous functioning of K+-channels and K+/H+-antiporter, and also Ca2+-uniporter together with MPTP as the cations influx and efflux pathways. Independent of MPTP opening, the activation of both constitutes of K+-cycle, K+-uptake as well as K+/H+-exchange, by DZ is observed. It is shown that the activation of transmembrane exchange of K+, combined with MPTP opening, results in partial inhibition of the latter. A simple methodical approach for the estimation of DZ influence on the open state of mitochondrial pore is proposed.
It is shown that MPTP closure followed by Ca2+ reentry to the matrix is accompanied by the K+/H+-exchange inhibition which takes place in the same timeframes as the increase in matrix Ca2+ content. Relevant to physiological conditions, an important physiological function of MPTP is revealed, that is the maintenance of relatively low matrix level of Ca2+ accompanied by the acceleration of transmembrane ion exchange (K+ and Ca2+) which could strongly influence the energy state and energy-dependent processes in mitochondria.

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