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

线粒体 ATP 敏感 K^ 通道的重塑响应心力衰竭和心房颤动

基本信息

批准号：
15590719
负责人：
SATO Toshiaki
金额：
$ 2.24万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590719/
关键词：
ATP-sensitive K^+ channel Mitochondria Heart failure Remodeling Protein kinase C

项目摘要

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.

众所周知，在心力衰竭和心房颤动期间发生离子通道的重构。然而，线粒体内膜ATP敏感性K^+通道（mitoK_channel）的重构<ATP>却知之甚少。本研究旨在了解心力衰竭时心肌线粒体K_<ATP>2通道的重构。从Bio 14.6心肌病仓鼠分离单个心室肌细胞，并使用二氮嗪氧化线粒体黄素蛋白来定量<ATP>mitoK_2通道活性。二氮嗪的应用引起氧化的黄素蛋白的潜伏期后，15分钟。在生物14.6心室肌细胞的反应的潜伏期显着大于在正常F1b仓鼠。然而，Bio 14.6心肌细胞中黄素蛋白氧化的程度与F1b心肌细胞中达到的程度相当。这些结果表明，<ATP>在心力衰竭过程中，mitoK_2通道的密度似乎没有改变。已<ATP>显示蛋白激酶C可增强mitoK1通道的开放。因此，我们研究了缓激肽激活蛋白激酶C是否调节<ATP>衰竭心肌细胞的线粒体K_通道。缓激肽增加线粒体K_<ATP>通道活性，缩短线粒体K_通道开放的潜伏期<ATP>。这些结果表明，受损的蛋白激酶C依赖的信号转导级联反应可能<ATP>在Bio 14.6心肌病仓鼠中继发性调节mitoK_2通道活性。