Influence of ATP-dependent K+-channel opener on K+-cycle and oxygen consumption in rat liver mitochondria

The influence of the K+(ATP)-channel opener diazoxide on the K+ cycle and oxygen consumption has been studied in rat liver mitochondria. It was found that diazoxide activates the K+(ATP)-channel in the range of nanomolar concentrations (50-300 nM, K(1/2) ~ 140 nM), which results in activation of K+/H+ exchange in mitochondria. The latter, in turn, accelerates mitochondrial respiration in respiratory state 2. The contribution of K+(ATP)-channel to the mitochondrial potassium cycle was estimated using the selective K+(ATP)-channel blocker glibenclamide. The data show that the relative contribution of K+(ATP)-channel in the potassium cycle of mitochondria is variable and increases only with the decrease in the ATP-independent component of K+ uptake. Possible mechanisms underlying the observed phenomena are discussed. The experimental results more fully elucidate the role of K+(ATP)-channel in the regulation of mitochondrial functions, especially under pathological conditions accompanied by impairment of the mitochondrial energy state.