Grover G J
Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Can J Physiol Pharmacol. 1997 Apr;75(4):309-15. doi: 10.1139/cjpp-75-4-309.
Recently, much interest has been focused on the pharmacology of ATP-sensitive potassium channels (KATP) in myocardial ischemia. KATP are thought to be involved with the mechanism of myocardial preconditioning, therefore further increasing the level of interest in these channels. Pharmacologic KATP openers have been shown by numerous investigators to protect ischemic-reperfused myocardium. These agents reduce necrosis, improve postischemic functional recovery, and inhibit contracture formation. These protective effects are abolished by KATP blockers. The cardioprotective effects of KATP openers are independent of vasodilator and cardiodepressant effects, but seem to be mediated by energy conservation (reduced ATP hydrolysis). Action potential shortening is also not correlated with cardioprotection, suggesting a role for intracellular (mitochondrial) KATP. Agents have been developed that retain the glyburide-reversible cardioprotective effects of cromakalim but are devoid of vasodilator and action potential shortening activity. Currently, studies are underway to determine the mechanism of cardioprotection. The potential role of mitochondrial KATP in the pathogenesis of ischemia is discussed in this review article.
最近，人们对心肌缺血时ATP敏感性钾通道（KATP）的药理学研究极为关注。KATP被认为与心肌预处理机制有关，因此进一步提高了人们对这些通道的兴趣。众多研究人员已证实，药理学上的KATP开放剂可保护缺血再灌注心肌。这些药物可减少坏死、改善缺血后功能恢复并抑制挛缩形成。KATP阻滞剂可消除这些保护作用。KATP开放剂的心脏保护作用与血管舒张和心脏抑制作用无关，但似乎是由能量守恒（减少ATP水解）介导的。动作电位缩短也与心脏保护无关，提示细胞内（线粒体）KATP发挥了作用。已研发出一些药物，它们保留了克罗卡林的格列本脲可逆性心脏保护作用，但没有血管舒张和动作电位缩短活性。目前，正在进行研究以确定心脏保护机制。本文综述讨论了线粒体KATP在缺血发病机制中的潜在作用。
