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

摘要

The influence of mitochondrial ATP-dependent Ksup+/sup-channel (Ksup+/supsubАТР/sub-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 Ksup+/sup– and Casup2+/sup-cycling supported by the simultaneous functioning of Ksup+/sup-channels and Ksup+/sup/Hsup+/sup-antiporter, and also Casup2+/sup-uniporter together with MPTP as the cations influx and efflux pathways. Independent of MPTP opening, the activation of both constitutes of Ksup+/sup-cycle, Ksup+/sup-uptake as well as Ksup+/sup/Hsup+/sup-exchange, by DZ is observed. It is shown that the activation of transmembrane exchange of Ksup+/sup, 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 Casup2+/sup reentry to the matrix is accompanied by the Ksup+/sup/Hsup+/sup-exchange inhibition which takes place in the same timeframes as the increase in matrix Casup2+/sup content. Relevant to physiological conditions, an important physiological function of MPTP is revealed, that is the maintenance of relatively low matrix level of Casup2+/sup accompanied by the acceleration of transmembrane ion exchange (Ksup+/sup and Casup2+/sup) which could strongly influence the energy state and energy-dependent processes in mitochondria.