Evidence for mitochondrial K+ channels and their role in cardioprotection.
Twenty years after the discovery of sarcolemmal ATP-sensitive K+ channels and 12 years after the discovery of mitochondrial K(ATP) (mitoK(ATP)) 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 mitoK(ATP), 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 mitoK(ATP) and highlights outstanding questions and controversies, with the intent of stimulating additional investigation on this topic.
Institute of Molecular Cardiobiology, Johns Hopkins University, 720 Rutland Ave, 844 Ross Bldg, Baltimore, Md 21205-2195, USA. bor@jhmi.edu
Brian
B
O'Rourke
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003981:Diazoxide / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D017136:Ion Transport; D019157:Ischemic Preconditioning, Myocardial; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008929:Mitochondria, Heart / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels; D051381:Rats
D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D000241:Adenosine; D003981:Diazoxide; D011188:Potassium