Role of the Mitochondrial Permeability Transition in Myocardial Disease Primary and Secondary Signaling Pathways in Early Preconditioning That Converge on the Mitochondria to Produce Cardioprotection Evidence for Mitochondrial K Channels and Their Role in Cardioprotection Mitochondrial Death Pathways

Twenty years after the discovery of sarcolemmal ATP-sensitive K channels and 12 years after the discovery of mitochondrial KATP (mitoKATP) channels, progress has been remarkable, but many questions remain. In the case of the former, detailed structural information is available, and it is well accepted that the channel couples bioenergetics to cellular electrical excitability; however, in the heart, a clear physiological or pathophysiological role has yet to be defined. For mitoKATP, structural information is lacking, but there is abundant evidence linking the opening of the channel to protection against ischemia-reperfusion injury or apoptosis. This review updates recent progress in understanding the physiological role of mitoKATP and highlights outstanding questions and controversies, with the intent of stimulating additional investigation on this topic. (Circ Res. 2004;94:420-432.)