Ukrains'kyi biokhimichnyi zhurnal (1999 )

[The effect of ATP-dependent K(+)-channel opener on the functional state and the opening of cyclosporine-sensitive pore in rat liver mitochondria].

PMID 23937047


The effect of mitochondrial ATP-dependent K(+)-channel (K+(ATP)-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+(ATP)-channel activation results in the increase of the oxygen consumption rate (V4(s)) 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+(ATP)-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 Ca(2+)-cycling supported by MPTP and Ca(2+)-uniporter as well as K(+)-channels and K+/H(+)-exchange. K+(ATP)-channel activation leads to the partial inhibition of MPTP, but insufficient for the restoration of mitochondrial functions. Elimination of Ca(2+)-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+(ATP)-channel activation.