THE INFLUENCE OF ATP-DEPENDENT K+-CHANNEL DIAZOXIDE OPENER ON THE OPENING OF MITOCHONDRIAL PERMEABILITY TRANSITION PORE IN RAT LIVER MITOCHONDRIA
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.
Key words: K+АТР-channel, diazoxide, Ca2+, K+, transport, mitochondrial permeability transition pore.
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