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首页> 外文期刊>American Journal of Physiology >Regulation of the cardiac L-type Ca2+ channel by the actin-binding proteins alpha-actinin and dystrophin.
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Regulation of the cardiac L-type Ca2+ channel by the actin-binding proteins alpha-actinin and dystrophin.

机译：肌动蛋白结合蛋白α-肌动蛋白和肌营养不良蛋白对心脏L型Ca2 +通道的调节。

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The actin-binding proteins dystrophin and alpha-actinin are members of a family of actin-binding proteins that may link the cytoskeleton to membrane proteins such as ion channels. Previous work demonstrated that the activity of Ca2+ channels can be regulated by agents that disrupt or stabilize the cytoskeleton. In the present study, we employed immunohistochemical and electrophysiological techniques to investigate the potential regulation of cardiac L-type Ca2+ channel activity by dystrophin and alpha-actinin in cardiac myocytes and in heterologous cells. Both actin-binding proteins were found to colocalize with the Ca2+ channel in mouse cardiac myocytes and to modulate channel function. Inactivation of the Ca2+ channel in cardiac myocytes from mice lacking dystrophin (mdx mice) was reduced compared with that in wild-type myocytes, voltage dependence of activation was shifted by 5 mV to more positive potentials, and stimulation by the beta-adrenergic pathway and the dihydropyridine agonist BAY K 8644 was increased. Furthermore, heterologous coexpression of the Ca2+ channel with muscle, but not nonmuscle, forms of alpha-actinin was also found to reduce inactivation. As might be predicted from a reduction of Ca2+ channel inactivation, a prolonging of the mouse electrocardiogram QT was observed in mdx mice. These results suggest a combined role for dystrophin and alpha-actinin in regulating the activity of the cardiac L-type Ca2+ channel and a potential mechanism for cardiac dysfunction in Duchenne and Becker muscular dystrophies.
机译：肌动蛋白结合蛋白肌营养不良蛋白和α-肌动蛋白是肌动蛋白结合蛋白家族的成员，可以将细胞骨架连接到膜蛋白，例如离子通道。先前的研究表明，Ca2 +通道的活性可以通过破坏或稳定细胞骨架的药物来调节。在本研究中，我们采用了免疫组织化学和电生理技术来研究肌营养不良蛋白和α-肌动蛋白在心肌细胞和异源细胞中对心脏L型Ca2 +通道活性的潜在调控。发现这两种肌动蛋白结合蛋白均与小鼠心肌细胞中的Ca2 +通道共定位并调节通道功能。与野生型心肌细胞相比，缺乏抗肌萎缩蛋白的小鼠（mdx小鼠）的心肌细胞中Ca2 +通道的失活减少，激活的电压依赖性转移了5 mV，变为更多的正电位，并且受到了β-肾上腺素能途径和增加了二氢吡啶激动剂BAY K 8644。此外，还发现Ca2 +通道与肌肉（而非非肌肉形式）的α-肌动蛋白异源共表达可减少失活。正如从Ca2 +通道失活的减少所预测的那样，在mdx小鼠中观察到了小鼠心电图QT的延长。这些结果表明，肌营养不良蛋白和α-肌动蛋白在调节心脏L型Ca2 +通道的活性中起着联合作用，并在杜兴氏和贝克尔肌营养不良中引起心脏功能障碍的潜在机制。

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