M itochondrial K channels : role in cardioprotectionATP

The role of the mitochondrial ATP-sensitive potassium channel (mK ) in ischemic preconditioning and cardioprotection is reviewed. ATP 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 opening causes mitochondria to generate reactive oxygen species (ROS) which then activate downstream kinases. Opening of ATP mK 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 ATP G -coupled receptors trigger protection through the mK /ROS pathway except for the adenosine receptor which uses some other, as yet i ATP unidentified, pathway. Possible coupling schemes between the receptors and the mK are discussed. Protection from preconditioning ATP can also be aborted when a mK blocker is present only during the lethal ischemic insult (mediator phase), but a much higher ATP concentration of the blocker is required. Thus the mK probably serves a dual role as both a trigger and a mediator. Possible ATP end-effectors of preconditioning’s protection are discussed including the mK itself. ATP  2002 Elsevier Science B.V. All rights reserved.