New aspects for the treatment of cardiac diseases based on the diversity of functional controls on cardiac muscles: mitochondrial ion channels and cardioprotection.
New aspects for the treatment of cardiac diseases based on the diversity of functional controls on cardiac muscles: mitochondrial ion channels and cardioprotection.
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DOI：
10.1254/jphs.08r24fm
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发表时间：
2009-03
影响因子：
3.5
通讯作者：
Hirofumi Nishida;Toshiaki Sato;T. Ogura;H. Nakaya
中科院分区：
文献类型：
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作者：
Hirofumi Nishida;Toshiaki Sato;T. Ogura;H. Nakaya
心肌细胞中存在线粒体ATP敏感性钾通道（mitoK（ATP））和钙激活性钾通道（mitoK（Ca）），它们在心肌保护中起重要作用。我们最近报道了通过mitoK（ATP）或mitoK（Ca）通道的K（+）内流彼此独立地发生，并以类似的方式赋予心脏保护作用。线粒体K（ATP）通道的激活被蛋白激酶C（PKC）增强，而线粒体K（Ca）通道被蛋白激酶A（PKA）激活。然而，磷脂酰肌醇3-激酶（PI 3-K）既不与线粒体K（ATP）通道连接，也不与线粒体K（Ca）通道连接。我们已经证明，生物活性物质通过PKC依赖性途径调节mitoK（ATP）通道的开放或通过PKC依赖性途径调节mitoK（Ca）通道的开放，从而保护心脏免受缺血/再灌注损伤。几种内源性物质如腺苷和缓激肽可以通过以PKC依赖性方式激活mitoK（ATP）通道来减小梗死面积。肾上腺髓质素是一种有效的血管扩张肽，通过PKA激活增强mitoK（Ca）通道的开放。在缺血前用肾上腺髓质素治疗通过PKA介导的mitoK（Ca）通道的激活导致梗死面积减小。因此，一些内源性物质通过PKA或PKC介导的mitoK（ATP）或mitoK（Ca）通道的激活来赋予心脏保护作用。
Mitochondrial ATP-sensitive K(+) (mitoK(ATP)) and Ca(2+)-activated K(+) (mitoK(Ca)) channels exist in cardiac myocytes, and they play key roles in cardioprotection. We have recently reported that K(+) influx through mitoK(ATP) or mitoK(Ca) channels occurs independently of each other and confers cardioprotection in a similar manner. Activation of mitoK(ATP) channel is augmented by protein kinase C (PKC), whereas mitoK(Ca) channel is activated by protein kinase A (PKA). However, phosphatidylinositol 3-kinase (PI3-K) is linked to neither mitoK(ATP) nor mitoK(Ca) channels. We have demonstrated that bioactive substances modulate the opening of mitoK(ATP) channels via a PKC-dependent pathway or opening of mitoK(Ca) channels via a PKA-dependent pathway and thereby protecting the heart from ischemia/reperfusion injury. Several endogenous substances such as adenosine and bradykinin can reduce infarct size by activation of mitoK(ATP) channels in a PKC-dependent manner. Adrenomedullin, a potent vasodilator peptide, potentiates the opening of mitoK(Ca) channels by PKA activation. Treatment with adrenomedullin prior to ischemia results in the reduction of infarct size via a PKA-mediated activation of mitoK(Ca) channels. Thus, some endogenous substances confer cardioprotection via PKA- or PKC-mediated activation of mitoK(ATP) or mitoK(Ca) channels.