Mitochondrial K(ATP) channels: role in cardioprotection.
The role of the mitochondrial ATP-sensitive potassium channel (mK(ATP)) in ischemic preconditioning and cardioprotection is reviewed. A great deal of accumulated evidence implicatese opening of this channel as an important step in the anti-infarct effect of ischemic preconditioning. Recent studies, however, reveal that channel opening can actually serve as a signal transduction element. Data indicate that mK(ATP) opening causes mitochondria to generate reactive oxygen species (ROS) which then activate downstream kinases. Opening of mK(ATP) prior to ischemia can serve as a trigger since the critical time for its opening is prior to the onset of the lethal ischemic insult. Most G(i)-coupled receptors trigger protection through the mK(ATP)/ROS pathway except for the adenosine receptor which uses some other, as yet unidentified, pathway. Possible coupling schemes between the receptors and the mK(ATP) are discussed. Protection from preconditioning can also be aborted when a mK(ATP) blocker is present only during the lethal ischemic insult (mediator phase), but a much higher concentration of the blocker is required. Thus the mK(ATP) probably serves a dual role as both a trigger and a mediator. Possible end-effectors of preconditioning's protection are discussed including the mK(ATP) itself.
Oldenburg
Olaf
O
Department of Physiology, MSB 3024, University of South Alabama, College of Medicine, Mobile 36688, USA.
Cohen
Michael V
MV
Yellon
Derek M
DM
Downey
James M
JM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D015221:Potassium Channels / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D015221:Potassium Channels; D017382:Reactive Oxygen Species; D018002:Receptors, Bradykinin; D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases