KATP Channels Functioning is Critical for Mitochondrial Bioenergetics under Physical Stress

Abstract

The modulation of mKATP channel activity is known to have a great impact on energy metabolism in a living organism. The aim of this work was to study the impact of mKATP channels opening on the physical endurance in the rats subject to compulsory swimming with a load. Our purpose was to find a mechanistic basis to explain the modulation of the energy metabolism under exercise training by studying the direct effect of mKATP channel opening on mitochondrial functions. Male Wistar rats exhibiting high and low resistance to physical stress were separated in two groups, and subjected to compulsory swimming with a load. Swimming time (ST) was monitored from the start till the fatigue was reached, and the rats began to drawn. ST was reliably higher in high resistance group, which coincided with higher endogenous mKATP channels activity. Unlike this, mKATP channels blockers, glibenclamide and 5-hydroxydecanoate completely blocked mKATP channel in vivo and dramatically reduced ST in both groups, which indicated its dependence on mKATP channel activity. To find a mechanistic basis for the observed dependence, we studied the effect of mKATP channels opening on mitochondrial functions in vitro. mKATP channels opener diazoxide stimulated state 4 respiration and decreased RCR, but increased phosphorylation efficiency (P/O). On the contrary, mKATP channels blockers, dramatically reduced P/O. Based on the experiments, we came to the conclusion of the correlation between the physical endurance and P/O ratio, both dependent on mKATP channels activity. Thus, mKATP channels opening inhibited phosphorylation, but increased its efficiency, which reduced energy expense for ATP synthesis. In vivo this resulted in the improvement of the endurance in the animals with elevated mKATP channel activity. Possible mechanisms and physiological relevance of the observed phenomena are discussed.