O. V. Akopova

Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
e-mail: luko@biph.kiev.ua

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.

Keywords: Ca2+, diazoxide, K(+), K(+)(АТР)-channel, mitochondrial permeability transition pore, transport