Opening mitochondrial K-ATP in the heart - what happens, and what does nothappen

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 cardiomyoc yte: How does opening mitoK(ATP) protect? What is the normal physiological role of mitoK(ATP) in the heart? Before these questions can be addressed, i t is necessary to agree on the bioenergetic consequences of opening mitoK(A TP) and this distills down to a single question - does opening mitoK(ATP) c ause 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, op ening mitoK(ATP) results in increased K+ flux that is sufficient to change mitochondrial volume but is insufficient to cause significant depolarizatio n of membrane potential. The volume changes, however, have significant bioe nergetic consequences for energy coupling in the cell.