Tag Archives: K(+)(АТР)-channel
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;
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.
The effect of ATP-dependent K(+)-channel opener on the functional state and the opening of cyclosporine-sensitive pore in rat liver mitochondria
O. V. Akopova, V. I. Nosar, V. A. Bouryi, L. I. Kolchinskaya,
I. N. Mankovska, V. F. Sagach
Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
e-mail: a-dubensky@mail.ru
The effect of mitochondrial ATP-dependent K+-channel (K+АТР-channel) opener diazoxide (DZ) on the oxygen consumption, functional state and the opening of cyclosporine-sensitive pore in the rat liver mitochondria has been studied. It has been established that K+АТР-channel activation results in the increase of the oxygen consumption rate (V4S) and the uncoupling due to the acceleration of K+-cycling, the decrease in state 3 respiration rate (V3) and the respiratory control ratio (RCR). Under K+АТР-channel activation an inhibition of oxidative phosphorylation takes place which reduces the rate of ATP synthesis and hydrolysis as well as ATP production and consequently results in the seeming increase of P/O ratio. It has been shown that the increase in ATP-dependent K+-uptake accompanied by the opening of mitochondrial permeability transition pore (MPTP) leads to dramatic uncoupling of the respiratory chain due to simultaneous activation of K+– and Ca2+-cycling supported by MPTP and Ca2+-uniporter as well as K+-channels and K+/H+-exchange. K+АТР-channel activation leads to the partial inhibition of MPTP, but insufficient for the restoration of mitochondrial functions. Elimination of Ca2+-cycling after MPTP opening is necessary to return mitochondrial functions back to the control level which shows that MPTP could serve as the mechanism of reversible modulation of bioenergetic effects of K+АТР-channel activation.