Catterall William A, Wisedchaisri Goragot, Zheng Ning
Department of Pharmacology, University of Washington, Seattle, Washington, USA.
Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
Nat Chem Biol. 2017 Apr 13;13(5):455-463. doi: 10.1038/nchembio.2353.
Electrical signals generated by minute currents of ions moving across cell membranes are central to all rapid processes in biology. Initiation and propagation of electrical signals requires voltage-gated sodium (Na) and calcium (Ca) channels. These channels contain a tetramer of membrane-bound subunits or domains comprising a voltage sensor and a pore module. Voltage-dependent activation occurs as membrane depolarization drives outward movements of positive gating changes in the voltage sensor via a sliding-helix mechanism, which leads to a conformational change in the pore module that opens its intracellular activation gate. A unique negatively charged site in the selectivity filter conducts hydrated Na or Ca rapidly and selectively. Ion conductance is terminated by voltage-dependent inactivation, which causes asymmetric pore collapse. This Review focuses on recent advances in structure and function of Na and Ca channels that expand our current understanding of the chemical basis for electrical signaling mechanisms conserved from bacteria to humans.
离子跨细胞膜流动产生的微小电流所生成的电信号，是生物学中所有快速过程的核心。电信号的起始和传播需要电压门控钠（Na）通道和钙（Ca）通道。这些通道包含由膜结合亚基或结构域组成的四聚体，其中包括一个电压感受器和一个孔道模块。当膜去极化通过滑动螺旋机制驱动电压感受器中正向门控变化向外移动时，会发生电压依赖性激活，这会导致孔道模块发生构象变化，从而打开其细胞内激活门。选择性过滤器中一个独特的带负电荷位点能够快速且选择性地传导水合Na或Ca。离子传导通过电压依赖性失活终止，电压依赖性失活会导致孔道不对称塌陷。本综述重点关注Na通道和Ca通道在结构与功能方面的最新进展，这些进展拓展了我们目前对从细菌到人类保守的电信号传导机制化学基础的理解。
