Oldenburg Olaf, Cohen Michael V, Yellon Derek M, Downey James M
Department of Physiology, MSB 3024, University of South Alabama, College of Medicine, Mobile 36688, USA.
Cardiovasc Res. 2002 Aug 15;55(3):429-37. doi: 10.1016/s0008-6363(02)00439-x.
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.
本文综述了线粒体ATP敏感性钾通道（mK(ATP)）在缺血预处理和心脏保护中的作用。大量累积证据表明，该通道的开放是缺血预处理抗梗死效应的重要步骤。然而，最近的研究表明，通道开放实际上可作为一种信号转导元件。数据显示，mK(ATP)开放会导致线粒体产生活性氧（ROS），进而激活下游激酶。缺血前mK(ATP)的开放可作为一个触发因素，因为其开放的关键时间在致命性缺血损伤发生之前。除了通过其他尚未明确的途径发挥作用的腺苷受体外，大多数G(i)偶联受体通过mK(ATP)/ROS途径触发保护作用。文中讨论了受体与mK(ATP)之间可能的偶联机制。当mK(ATP)阻滞剂仅在致命性缺血损伤期间（介导期）存在时，预处理的保护作用也可能被取消，但所需阻滞剂浓度要高得多。因此，mK(ATP)可能兼具触发因素和介导因素的双重作用。文中还讨论了预处理保护作用可能的终效应器，包括mK(ATP)本身。
