Mechanosensitive Ion Channels in Cardiovascular Physiology

Mechanosensitive Ion Channels in Cardiovascular Physiology
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发表时间:
2014-09
影响因子:
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通讯作者:
J. Teng;S. Loukin;C. Kung
J. Teng;S. Loukin;C. Kung
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文献类型:
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作者:
J. Teng;S. Loukin;C. Kung

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EC偶联受到机械反馈的影响,这种反馈来自心包和其他部位的物理力敏感离子通道。本文综述了机械敏感(MS)通道的最新进展,包括TRPs和K2p。膜片钳通过膜拉伸直接激活通道。结晶学和冷冻电子显微镜揭示了几个原子分辨率的MS通道的结构。有些已经纯化到均一,重组成脂双分子层,仍然保持着对拉力的反应能力。一种来自脂类的作用力(FFL)理论强调了通道蛋白和脂类之间的强结合。通过这些键,双层的急剧横向张力(类似于表面张力)可以向通道蛋白传递额外的力。像温度敏感性一样,对机械力的敏感性比我们之前意识到的要普遍得多,对跳动的心脏尤其重要。
EC coupling is subjected to a mechanical feedback, which originates from physical force-sensing ion channels in the pericardium and elsewhere. Reviewed here are the most recent developments that greatly advanced our understanding of these mechanosensitive (MS) channels, including TRPs and K2p’s. Patch clamp has continued to demonstrate the direct channel activation by membrane stretch. Crystallography and cryo-electron microscopy have revealed the structures of several MS channels at atomic resolution. Some have been purified to homogeneity, reconstituted into lipid bilayer, and still retain their ability to respond to stretch force. A force-from-lipid (FFL) theory has been advanced that emphasizes the strong binding between channel proteins and lipids. Through these bonds, the sharp lateral tension (akin to surface tension) of the bilayer can transmit added force to the channel protein. Like temperature sensitivity, sensitivity to mechanical force is far more pervasive than we previously realize, and is especially important to the beating heart.