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DOI	10.1073/pnas.2017168118
	Conductance selectivity of Na+ across the K+ channel via Na+ trapped in a tortuous trajectory
	Mita K.; Sumikama T.; Iwamoto M.; Matsuki Y.; Shigemi K.; Oiki S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:12
英文摘要	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.
英文关键词	conductance ratio; KcsA channel; lipid bilayer; MD simulation; single-channel current
语种	英语
scopus关键词	carbon dioxide; carboxyl radical; potassium; potassium channel; sodium; cell membrane permeability; channel gating; chemistry; conformation; metabolism; molecular dynamics; structure activity relation; Carbon Dioxide; Cell Membrane Permeability; Ion Channel Gating; Molecular Conformation; Molecular Dynamics Simulation; Potassium; Potassium Channels; Sodium; Structure-Activity Relationship
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238593
作者单位	Department of Molecular Physiology and Biophysics, Faculty of Medical Sciences, University of FukuiFukui 910-1193, Japan; Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, University of FukuiFukui 910-1193, Japan; WPI Nano Life Science Institute, Kanazawa University, Kanazawa, 920-1192, Japan; Department of Molecular Neuroscience, Faculty of Medical Sciences, University of FukuiFukui 910-1193, Japan; Department of Molecular Physiology and Biophysics, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan;; Biomedical Imaging Research Center, University of FukuiFukui 910-1193, Japan
推荐引用方式 GB/T 7714	Mita K.,Sumikama T.,Iwamoto M.,et al. Conductance selectivity of Na+ across the K+ channel via Na+ trapped in a tortuous trajectory[J],2021,118(12).
APA	Mita K.,Sumikama T.,Iwamoto M.,Matsuki Y.,Shigemi K.,&Oiki S..(2021).Conductance selectivity of Na+ across the K+ channel via Na+ trapped in a tortuous trajectory.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Mita K.,et al."Conductance selectivity of Na+ across the K+ channel via Na+ trapped in a tortuous trajectory".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).