Structure and function of voltage-gated ion channels
Structure and function of voltage-gated ion channels
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DOI：
10.1016/0166-2236(93)90193-p
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发表时间：
1993-12
影响因子：
15.9
通讯作者：
W. Catterall
中科院分区：
文献类型：
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作者：
W. Catterall
电压门控的Na÷、Ca z÷和K÷通道的主要亚基是一个相关基因家族的成员，在电压依赖性激活、离子电导和h~激活中具有功能自主。在本文中，最近的工作定位负责这三个基本功能的电压门控离子通道的结构元件进行了回顾。这些研究揭示了不同离子通道之间强大的功能相似性，并表明它们性质的显著差异源于共同结构和功能主题的变化。电压门控离子通道在神经元和其他可兴奋细胞中负责传导电信号的产生。离子通透性的增加是由激活这些通道引起的。在去极化后，对Na+， Ca2+或K+的渗透率在0.5至数百毫秒的时间内急剧增加，然后在2毫秒至秒的时间内下降到基线水平。这种双相行为源于控制离子通道功能的两个实验可分离的门控过程：激活，控制去极化后渗透率增加的速率和电压依赖性，失活，控制在维持去极化期间离子渗透率随后返回到静息水平的速率和电压依赖性。活化离子通道的离子电导具有高度的选择性和显著的效率。生理离子的选择性范围从Na+通道对Na t的选择性是其他任何离子的12倍，到Ca 2÷通道对Ca+的选择性是Ca+的1000倍。所有这三种类型的离子通道都以接近其在自由溶液中扩散的速率传导离子穿过生物膜。了解电压依赖性激活、快速失活以及选择性和高效离子电导的分子基础是当前对这些关键信号蛋白研究的主要目标。
The principal subunits of the voltage-gated Na÷, Ca z÷ and K÷ channels are members of a related gene family and are functionally autonomous in voltage-dependent activation, ion conductance and h~ activation. In this article, recent work locating the structural elements that are responsible for these three basic functions of the voltage-gated ion channels is reviewed. These studies reveal strong functional analogies among the different ion channels and suggest that the striking differences in their properties arise as variations on a common structural and functional theme.The voltage-gated ion channels are responsible for the generation of conducted electrical signals in neurons and other excitable cells. The ion permeability increase resulting from activation of these channels is biphasic. Upon depolarization, permeability to Na+, Ca2+ or K+ increases dramatically over a period of 0.5 to hundreds of milliseconds and then decreases to the baseline level over a period of 2 ms to seconds. This biphasic behavior results from two experimentally separable gating processes that control ion channel function: activation, which controls the rate and voltage dependence of the permeability increase following depolarization, and inactivation, which controls the rate and voltage dependence of the subsequent return of the ion permeability to the resting level during a maintained depolarization. The ion conductance of the activated ion channels is both highly selective and remarkably efficient. Selectivity among the physiological ions ranges from Na+ channels being 12 times more selective for Na t than for any other ion, to Ca 2÷ channels that are 1000 times more selective for Ca+. All three classes of ion channels conduct ions across biological membranes at rates approaching their rates of diffusion through free solution. Understanding the molecular bases for voltage-dependent activation, rapid inactivation, and selective and efficient ion conductance is a major goal of current research on these critical signaling proteins.