Department of Molecular Physiology and Biophysics, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan.
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
J Physiol Sci. 2019 Nov;69(6):919-930. doi: 10.1007/s12576-019-00706-4. Epub 2019 Aug 27.
The mechanism underlying ion permeation through potassium channels still remains controversial. K ions permeate across a narrow selectivity filter (SF) in a single file. Conventional scenarios assume that K ions are tightly bound in the SF, and, thus, they are displaced from their energy well by ion-ion repulsion with an incoming ion. This tight coupling between entering and exiting ions has been called the "knock-on" mechanism. However, this paradigm is contradicted by experimental data measuring the water-ion flux coupling ratio, demonstrating fewer ion occupancies. Here, the results of molecular dynamics simulations of permeation through the KcsA potassium channel revealed an alternative mechanism. In the aligned ions in the SF (an ion queue), the outermost K was readily and spontaneously released toward the extracellular space, and the affinity of the relevant ion was ~ 50 mM. Based on this low-affinity regime, a simple queueing mechanism described by loose coupling of entering and exiting ions is proposed.
钾通道离子渗透的机制仍然存在争议。钾离子通过狭窄的选择性过滤器（SF）以单一行列的形式渗透。传统的情景假设钾离子在 SF 中紧密结合，因此，它们会受到进入离子的离子排斥而从能量阱中被取代。这种进入离子和离开离子之间的紧密耦合被称为“撞击”机制。然而，实验数据测量水离子通量偶联比，证明了较少的离子占据数，这与这一范式相矛盾。在这里，通过 KcsA 钾通道渗透的分子动力学模拟的结果揭示了一种替代机制。在 SF 中的对齐离子（离子队列）中，最外层的 K 很容易自发地朝向细胞外空间释放，相关离子的亲和力约为 50 mM。基于这种低亲和力状态，提出了一种简单的队列机制，描述了进入离子和离开离子的松散耦合。
