Mitochondrial K-ATP channels: role in cardioprotection.
429 - 437.
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. (C) 2002 Elsevier Science B.V. All rights reserved.
|Title:||Mitochondrial K-ATP channels: role in cardioprotection|
|Keywords:||free radicals, K-ATP channel, mitochondria, preconditioning, signal transduction, PROTEIN-KINASE-C, DEPENDENT POTASSIUM CHANNELS, GENERATING FREE-RADICALS, TYROSINE KINASE, ISCHEMIC MYOCARDIUM, POSSIBLE MECHANISM, ENERGY-METABOLISM, OXYGEN RADICALS, RABBIT HEARTS, CA2+ OVERLOAD|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
Archive Staff Only