Advances in CaV1.1 gating: New insights into permeation and voltage-sensing mechanisms.

Hugo Bibollet, Audra Kramer, Roger A Bannister, Erick O Hernández-Ochoa
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Abstract

The CaV1.1 voltage-gated Ca2+ channel carries L-type Ca2+ current and is the voltage-sensor for excitation-contraction (EC) coupling in skeletal muscle. Significant breakthroughs in the EC coupling field have often been close on the heels of technological advancement. In particular, CaV1.1 was the first voltage-gated Ca2+ channel to be cloned, the first ion channel to have its gating current measured and the first ion channel to have an effectively null animal model. Though these innovations have provided invaluable information regarding how CaV1.1 detects changes in membrane potential and transmits intra- and inter-molecular signals which cause opening of the channel pore and support Ca2+ release from the sarcoplasmic reticulum remain elusive. Here, we review current perspectives on this topic including the recent application of functional site-directed fluorometry.

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CaV1.1门控的新进展:渗透和电压传感机制的新见解。
CaV1.1电压门控Ca2+通道携带L型Ca2+电流,是骨骼肌兴奋-收缩(EC)耦合的电压传感器。EC耦合领域的重大突破往往紧跟着技术进步。特别地,CaV1.1是第一个被克隆的电压门控Ca2+通道,第一个测量其门控电流的离子通道,以及第一个具有有效无效动物模型的离子通道。尽管这些创新提供了关于CaV1.1如何检测膜电位变化并传递分子内和分子间信号的宝贵信息,这些信号导致通道孔打开并支持Ca2+从肌浆网释放,但仍然难以捉摸。在这里,我们回顾了当前对这一主题的看法,包括功能位点导向荧光测定法的最新应用。
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