Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide: A 2020 Update

Diazoxide (DZ) is a well-known cardioprotective drug that works in the same way as ischemic preconditioning. DZ is primarily a pharmacological opener of mitochondrial ATP-sensitive potassium channels (mKATP channels), but its interactions with other cellular targets (such as plasma membrane KATP channels, F0F1 ATP synthase, succinate dehydrogenase, and others) are known to cause several side effects, potentially confounding understanding of the direct bioenergetic effects of mKATP channels. The direct and off-target effects of DZ were addressed in this study. DZ interactions with mKATP channels, as well as DZ interactions with other molecular targets affecting mitochondrial functions and bioenergetics, are discussed. The conclusion was reached that the high sensitivity of the mKATP channel to DZ demonstrated in our studies allows for the avoidance of off-target effects of this drug in isolated mitochondria studies, making it a valuable tool for assessing the various functional effects of mKATP channel opening.

Author (s) Details

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

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