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

众所周知，离子通道的重构发生在心力衰竭和房颤的过程中。然而，线粒体内膜上ATP敏感性钾离子通道(mitoK&lt；ATP&gt；通道)的重构却知之甚少。本研究旨在了解心力衰竭对心肌细胞线粒体K_1、ATP和GT_1通道的影响。从Bio 14.6心肌病仓鼠分离单个心室肌细胞，用二氮嗪氧化线粒体黄素蛋白来定量mitoK通道活性。应用二氮嗪后，黄素蛋白在约15min的潜伏期后被氧化。Bio 14.6心肌细胞的反应潜伏期明显长于正常F1B仓鼠。然而，Bio 14.6心肌细胞的黄素蛋白氧化程度与F1B心肌细胞相当。这些结果表明，在心力衰竭过程中，线粒体K通道的密度似乎没有改变。我们因此研究了缓激肽激活蛋白激酶C是否调节衰竭心肌细胞的mitoK；；ATP&gt；通道。缓激肽增加mitoK；ATP；通道活性，缩短潜伏期至mitoK；ATP；通道开放。这些结果表明，受损的蛋白激酶C依赖的信号转导通路可能对Bio 14.6心肌病仓鼠的mitoK_1；ATP&gt；通道活动进行继发性调节。

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.