Department of Chemistry Biology and Biotechnology, University of Perugia, Perugia, Italy.
Department of Physics, University of Genova, Genova, Italy.
J Gen Physiol. 2023 Aug 7;155(8). doi: 10.1085/jgp.202313380. Epub 2023 Jul 6.
We celebrate this year the 50th anniversary of the first electrophysiological recordings of the gating currents from voltage-dependent ion channels done in 1973. This retrospective tries to illustrate the context knowledge on channel gating and the impact gating-current recording had then, and how it continued to clarify concepts, elaborate new ideas, and steer the scientific debate in these 50 years. The notion of gating particles and gating currents was first put forward by Hodgkin and Huxley in 1952 as a necessary assumption for interpreting the voltage dependence of the Na and K conductances of the action potential. 20 years later, gating currents were actually recorded, and over the following decades have represented the most direct means of tracing the movement of the gating charges and gaining insights into the mechanisms of channel gating. Most work in the early years was focused on the gating currents from the Na and K channels as found in the squid giant axon. With channel cloning and expression on heterologous systems, other channels as well as voltage-dependent enzymes were investigated. Other approaches were also introduced (cysteine mutagenesis and labeling, site-directed fluorometry, cryo-EM crystallography, and molecular dynamics [MD] modeling) to provide an integrated and coherent view of voltage-dependent gating in biological macromolecules. The layout of this retrospective reflects the past 50 years of investigations on gating currents, first addressing studies done on Na and K channels and then on other voltage-gated channels and non-channel structures. The review closes with a brief overview of how the gating-charge/voltage-sensor movements are translated into pore opening and the pathologies associated with mutations targeting the structures involved with the gating currents.
我们今年庆祝 1973 年首次记录电压门控离子通道门控电流的 50 周年。这篇回顾性文章试图说明通道门控的背景知识,以及门控电流记录当时的影响,以及它如何在这 50 年中继续阐明概念、阐述新想法,并引导科学辩论。门控粒子和门控电流的概念最初是由 Hodgkin 和 Huxley 在 1952 年提出的,作为解释动作电位中 Na 和 K 电导的电压依赖性的必要假设。20 年后,实际上记录了门控电流,在接下来的几十年里,它一直是追踪门控电荷运动并深入了解通道门控机制的最直接手段。早期的大部分工作都集中在鱿鱼巨大轴突中发现的 Na 和 K 通道的门控电流上。随着通道克隆和异源系统表达,其他通道以及电压依赖性酶也得到了研究。还引入了其他方法(半胱氨酸诱变和标记、定点荧光法、冷冻电镜晶体学和分子动力学 [MD] 建模),以提供对生物大分子中电压依赖性门控的综合和连贯的观点。这篇回顾性文章的布局反映了过去 50 年来对门控电流的研究,首先是关于 Na 和 K 通道的研究,然后是关于其他电压门控通道和非通道结构的研究。综述最后简要概述了门控电荷/电压传感器的运动如何转化为孔的打开,以及针对涉及门控电流的结构的突变相关的病理学。