Department of Molecular Physiology and Biophysics, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Proc Natl Acad Sci U S A. 2021 Mar 23;118(12). doi: 10.1073/pnas.2017168118.
Ion selectivity of the potassium channel is crucial for regulating electrical activity in living cells; however, the mechanism underlying the potassium channel selectivity that favors large K over small Na remains unclear. Generally, Na is not completely excluded from permeation through potassium channels. Herein, the distinct nature of Na conduction through the prototypical KcsA potassium channel was examined. Single-channel current recordings revealed that, at a high Na concentration (200 mM), the channel was blocked by Na, and this blocking was relieved at high membrane potentials, suggesting the passage of Na across the channel. At a 2,000 mM Na concentration, single-channel Na conductance was measured as one-eightieth of the K conductance, indicating that the selectivity filter allows substantial conduit of Na Molecular dynamics simulations revealed unprecedented atomic trajectories of Na permeation. In the selectivity filter having a series of carbonyl oxygen rings, a smaller Na was distributed off-center in eight carbonyl oxygen-coordinated sites as well as on-center in four carbonyl oxygen-coordinated sites. This amphipathic nature of Na coordination yielded a continuous but tortuous path along the filter. Trapping of Na in many deep free energy wells in the filter caused slow elution. Conversely, K is conducted via a straight path, and as the number of occupied K ions increased to three, the concerted conduction was accelerated dramatically, generating the conductance selectivity ratio of up to 80. The selectivity filter allows accommodation of different ion species, but the ion coordination and interactions between ions render contrast conduction rates, constituting the potassium channel conductance selectivity.
钾通道的离子选择性对于调节活细胞中的电活动至关重要；然而，有利于大 K 而不是小 Na 通过的钾通道选择性的机制仍不清楚。通常，Na 不能完全被钾通道阻止通过。在此，研究了原型 KcsA 钾通道中 Na 传导的独特性质。单通道电流记录显示，在高 Na 浓度（200mM）下，通道被 Na 阻断，而在高膜电位下，这种阻断被解除，表明 Na 通过通道穿过。在 2000mM Na 浓度下，单通道 Na 电导被测量为 K 电导的八分之一，表明选择性过滤器允许 Na 大量通过。分子动力学模拟揭示了 Na 渗透前所未有的原子轨迹。在具有一系列羰基氧环的选择性过滤器中，较小的 Na 分布在八个羰基氧配位位的非中心位置以及四个羰基氧配位位的中心位置。Na 配位的这种两亲性产生了沿着过滤器的连续但曲折的路径。Na 在过滤器中的许多深自由能阱中被捕获导致洗脱缓慢。相反，K 通过直线路径传导，并且随着占据的 K 离子数量增加到三个，协同传导被显著加速，产生高达 80 的传导选择性比。选择性过滤器允许不同离子物种的适应，但离子配位和离子之间的相互作用导致对比传导率，构成了钾通道传导选择性。
