抗心肌缺血药物的新靶点:线粒体ATP敏感性钾通道

A new target for anti-ischemic drugs: mitochondrial ATP-sensitive potassium channel

ATP敏感性钾通道 (KATP)是心脏保护作用的调节位点。随着KATP药理学和分子生物学特征的深入研究 ,发现KATP开放剂介导的心脏保护机制并不依赖于动作电位时程(APD)的缩短和负性肌力作用 ,而与线粒体功能有关。细胞内存在线粒体KATP(mitoKATP)。mitoKATP开放的心脏保护作用机制尚不十分清楚 ,可能与K+ 内流 ,线粒体膜去极化 ,降低Ca2 + 超载 ,基质容积增加有关 ,后者可增加ATP合成。

ATP sensitive potassium channels (K ATP ) have been thought to be a mediator of cardioprotection. Recent pharmacologic and molecular biology studies show the protective effects of K ATP openers are not dependent of action potential shortening and cardiodepressant effects, but mediated by preservation of mitochondrial function, which suggests a role for intracellular mitochondrial K ATP (mito K ATP ). The mechanism by opening mito K ATP produces cardioprotection is less clearer, however, it is thought that a beneficial effect may occur as the result of K + entry and intramitochondrial depolarization. This effect would reduce mitochondrial calcium overload and cause matrix swelling, which are shown to enhance ATP synthesis and stimulate mitochondrial respiration.