The effect of atp-dependent potassium uptake on mitochondrial functions under acute hypoxia

The opening of mitochondrial K+ (DD cent D) -channel (mtK(+) (DD cent D) -channel) is supposed to be important in the modulation of mitochondrial functions under hypoxia, but the underlying mechanisms have not been clarified yet. The aim of this work was to study the effect of acute hypoxia on mtK(+) (DD cent D) -channel activity and to estimate the contribution of the channel in the modulation of mitochondrial functions. MtK(+) (DD cent D) -channel activity was assessed polarographically from the rate of State 4 respiration and by potentiometric monitoring of potassium efflux from deenergized mitochondria. It was shown that hypoxia reliably increased mtK(+) (DD cent D) -channel activity, which resulted in the changes of respiration rates (increase of State 4 and suppression of State 3 respiration), uncoupling (the decrease of respiratory control ratio) and suppression of phosphorylation. These effects were well mimicked by mtK(+) (DD cent D) -channel opener diazoxide (DZ) in isolated rat liver mitochondria. MtK(+) (DD cent D) -channel opening in vitro suppressed phosphorylation too, but increased phosphorylation efficiency, while mtK(+) (DD cent D) -channel blockers reduced it dramatically. The correlation was established between mtK(+) (DD cent D) -channel activity and the endurance of the rats to physical training under hypoxia. Hypoxia improved physical endurance, but treatment by mtK(+) (DD cent D) -channel blockers glibenklamide and 5-hydroxydecanoate (5-HD) prior to hypoxia strongly reduced both the channel activity and the endurance limits. This was in accord with the observation that under glibenklamide and 5-HD administration hypoxia failed to restore mtK(+) (DD cent D) -channel activity. Based on the experiments, we came to the conclusion that mtK(+) (DD cent D) -channel opening played a decisive role in the regulation of energy metabolism under acute hypoxia via the modulation of phosphorylation system in mitochondria.