Remodeling of mitochondrial ATP-sensitive K^+ channels in response to heart failure and atrial fibrillation

众所周知，离子通道重构发生在心力衰竭和心房颤动期间。然而，线粒体膜内ATP敏感的K^+通道（mitoK_<ATP>通道）的重塑机制尚不清楚。本研究旨在了解心力衰竭对心肌mitoK_<ATP>通道的影响。从bio14.6型心肌病仓鼠中分离单个心室肌细胞，采用线粒体黄蛋白氧化法测定线粒体mitoK_<ATP>通道活性。二氮氧化合物的应用在15min后引起了黄蛋白的氧化。Bio 14.6心室肌细胞的反应潜伏期明显大于正常F1b仓鼠。然而，Bio 14.6心肌细胞中的黄蛋白氧化程度与F1b心肌细胞中达到的程度相当。这些结果表明，mitoK_<ATP>通道的密度在心力衰竭期间似乎没有改变。蛋白激酶C可增强mitoK_<ATP>通道的打开。因此，我们研究了缓激肽激活蛋白激酶C是否可调节衰竭心肌细胞的mitoK_<ATP>通道。缓激素增加了mitoK_<ATP>通道的活性，缩短了mitoK_<ATP>通道开放的潜伏期。这些结果表明，受损的蛋白激酶c依赖性信号转导级联可能继发性地调节Bio 14.6心肌病仓鼠mitoK_<ATP>通道活性。

It is well known that the remodeling of ion channels occurs during heart failure and atrial fibrillation. However, the remodeling of ATP-sensitive K^+ channel in inner mitochondrial membrane (mitoK_<ATP> channel) is poorly understood. This study was undertaken to know cardiac mitoK_<ATP> channels are remodeled by heart failure. Single ventricular myocytes were isolated from Bio 14.6 cardiomyopathic hamsters and the mitochondrial flavoprotein oxidation by diazoxide was used to quantify mitoK_<ATP> channel activity. The application of diazoxide elicited oxidation of flavoprotein after a latency of 〜15 min. The latency of the response in Bio 14.6 ventricular myocytes was significantly greater than that in normal F1b hamsters. However, the degree of flavoprotein oxidation in Bio 14.6 cardiomyocytes was comparable to that achieved in F1b cardiomyocytes. These results suggest that the density of mitoK_<ATP> channels seems to be unaltered during heart failure. Opening of mitoK_<ATP> channels has been shown to be potentiated by protein kinase C. We therefore examined if activation of protein kinase C by bradykinin modulates mitoK_<ATP> channel in failing cardiomyocytes. Bradykinin increased mitoK_<ATP> channel activity and abbreviated the latency to mitoK_<ATP> channel opening. These results suggest that the impaired protein kinase C-dependent signal transduction cascade may secondarily modulate the mitoK_<ATP> channel activity in Bio 14.6 cardiomyopathic hamsters.