Role of Kir6.1 channels in cardiomyocytes clarified by Kir6.1-transgenic mice

心脏ATP敏感通道（K_<ATP>）是由成孔亚基Kir6.2和调节亚基磺酰脲受体（SUR2A）组成的异八聚体。尽管另一种成孔亚基Kir6.1据报道存在于心脏细胞中，但其在心脏中的病理生理意义尚不清楚。本研究利用过表达Kir6.1基因的转基因小鼠（Kir6.1 tg）在心肌组织中评价心脏Kir6.1蛋白的作用。野生型（WT）和Kir6.1TG小鼠langendorff灌注心脏全脑缺血（25 min），再灌注（120 min）。用三苯四唑染色法测定，与WT相比，Kir6.1TG心肌梗死面积更小，心肌收缩功能恢复更大。在Kir6.1TG小鼠冠状动脉灌注心室肌制剂中，动作电位持续时间（APD）比WT制剂在缺血前期更长，可能与K^+通道下调有关。在缺血时，Kir6.1TG制剂加速APD缩短。Kir6.1TG与WT心肌细胞线粒体K_<ATP>通道活性（通过二氮氧化物诱导的黄蛋白氧化间接评价）无显著差异。这些发现提示心肌细胞中的Kir6.1蛋白对心肌缺血/再灌注损伤具有保护作用。

It is acknowledged that cardiac ATP-sensitive (K_<ATP>) channel is a hetero-octamer comprising the pore-forming subunit Kir6.2 and the regulatory subunit sulfonylurea receptor (SUR2A). Although another pore-forming subunit Kir6.1 reportedly exists in heart cells, the pathophysiological significance of Kir6.1 in the heart remains unclear. This study was undertaken to evaluate the role of cardiac Kir6.1 protein using transgenic mice overexpressing Kir6.1 gene (Kir6.1TG) in the myocardium. Langendorff-perfused hearts of wild-type (WT) and Kir6.1TG mice were subjected to global ischemia (25 min) followed by reperfusion (120 min). Myocardial infarct size, measured by triphenyltetrazolium chloride staining, in Kir6.1TG hearts was smaller and recovery of contractile function of Kir6.1TG hearts was greater compared with WT hearts. In coronary-perfused ventricular muscle preparations of Kir6.1TG mice, the action potential duration (APD) was longer than that of WT preparations in pre-ischemic period, probably due to downregulation of K^+ channels. During ischemia the APD shortening was accelerated in Kir6.1TG preparations. There was no difference in mitochondrial K_<ATP> channel activity, which was indirectly evaluated by diazoxide-induced flavoprotein oxidation, between Kir6.1TG and WT cardiomyocytes. These findings suggest that Kir6.1 protein in cardiomyocytes affords cardioprotection against ischemia/reperfusion injury.