KATP Channels Functioning is Critical for Mitochondrial Bioenergetics under Physical Stress

The modification of mKATP channel activity in a living organism is known to have a significant impact on energy metabolism. The goal of this study was to see how opening mKATP channels affected physical endurance in rats who were forced to swim with a burden. Our goal was to investigate the direct influence of mKATP channel opening on mitochondrial processes in order to uncover a molecular foundation for explaining the modification of energy metabolism during exercise training. Male Wistar rats with strong and low resilience to physical stress were placed into two groups and required to swim with a burden. The swimming time (ST) was recorded from the beginning until the rats were fatigued and began to sketch. ST was consistently higher in the high resistance group, which corresponded to increased activation of endogenous mKATP channels. mKATP channel blockers such as glibenclamide and 5-hydroxydecanoate, on the other hand, totally inhibited the mKATP channel in vivo and significantly lowered ST in both groups, indicating its reliance on mKATP channel activity. We investigated the influence of mKATP channel opening on mitochondrial activities in vitro to establish a molecular explanation for the observed dependence. State 4 respiration was enhanced by mKATP channel opener diazoxide, which decreased RCR but increased phosphorylation efficiency (P/O). mKATP channel blockers, on the other hand, significantly lowered P/O. Based on the results of the studies, we discovered a link between physical endurance and P/O ratio, both of which are influenced by the activation of mKATP channels. As a result, activating mKATP channels hindered phosphorylation but increased its efficiency, lowering the energy cost of ATP generation. In animals with increased mKATP channel activity, this resulted in improved endurance in vivo. The observed phenomena’s possible explanations and physiological relevance are addressed.
Author (S) Details

Olga Akopova
Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.

Iryna Mankovska
Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.

Valentina Nosar
Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine and International Centre for Astronomical, Medical and Ecological Research NAS of Ukraine, Kiev, Ukraine.

Liudmila Kolchinskaya
Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.

Vadim Sagach
Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.

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