Opening mitochondrial K_ATP in the heart – what happens, and what does not happen

Abstract

There is considerable evidence that opening the mitochondrial ATP-sensitive potassium channel (mitoK_ATP) is cardioprotective in ischemia-reperfusion. Two prominent questions surround the role of mitoK_ATP in the cardiomyocyte: How does opening mitoK_ATP protect? What is the normal physiological role of mitoK_ATP in the heart? Before these questions can be addressed, it is necessary to agree on the bioenergetic consequences of opening mitoK_ATP, and this distills down to a single question – does opening mitoK_ATP cause significant uncoupling or not? The evidence strongly indicates that it does not and that reports of uncoupling and inhibition of Ca²⁺ uptake are the result of using toxic concentrations of K_ATP channel openers. Thus, opening mitoK_ATP results in increased K⁺ flux that is sufficient to change mitochondrial volume but is insufficient to cause significant depolarization of membrane potential. The volume changes, however, have significant bioenergetic consequences for energy coupling in the cell.