Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes
Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes
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一氧化碳抑制心肌细胞内向整流钾通道
DOI：
10.1038/ncomms5676
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Gu, Yuchun
中科院分区：
文献类型：
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作者：
Liang, Shenghui;Wang, Quanyi;Gu, Yuchun
心肌梗死后再灌注诱发的心室颤动（VF）严重威胁着患者的生命。一氧化碳（CO）-产生血红素氧合酶在心肌细胞-已被报道，以防止VF通过一个未知的作用机制。在这里，我们报告，CO通过抑制内向整流钾（Kir）通道的一个子集来缩短动作电位时程（APD）。我们发现，CO块Kir2.2和Kir2.3，但不Kir2.1通道在心肌细胞和HEK-293细胞转染Kir。CO通过干扰Kir2.3与第二信使磷脂酰肌醇（4，5）-二磷酸（PIP 2）的相互作用而直接抑制Kir2.3。由于CO对心肌细胞中Kir2.2和Kir2.3的抑制作用，心脏Kir2.2和Kir2.3是预防再灌注诱导VF的有希望的靶点。
Reperfusion-induced ventricular fibrillation (VF) severely threatens the lives of post-myocardial infarction patients. Carbon monoxide (CO)-produced by haem oxygenase in cardiomyocytes-has been reported to prevent VF through an unknown mechanism of action. Here, we report that CO prolongs action potential duration (APD) by inhibiting a subset of inward-rectifying potassium (Kir) channels. We show that CO blocks Kir2.2 and Kir2.3 but not Kir2.1 channels in both cardiomyocytes and HEK-293 cells transfected with Kir. CO directly inhibits Kir2.3 by interfering with its interaction with the second messenger phosphatidylinositol (4,5)-bisphosphate (PIP2). As the inhibition of Kir2.2 and Kir2.3 by CO prolongs APD in myocytes, cardiac Kir2.2 and Kir2.3 are promising targets for the prevention of reperfusion-induced VF.