title: Ion Concentration- and Voltage-Dependent Push and Pull Mechanisms of Potassium Channel Ion Conduction.
abstract: The mechanism of ion conduction by potassium channels is one of the central issues in physiology. In particular, it is still unclear how the ion concentration and the membrane voltage drive ion conduction. We have investigated the dynamics of the ion conduction processes in the Kv1.2 pore domain, by molecular dynamics (MD) simulations with several different voltages and ion concentrations. By focusing on the detailed ion movements through the pore including selectivity filter (SF) and cavity, we found two major conduction mechanisms, called the III-IV-III and III-II-III mechanisms, and the balance between the ion concentration and the voltage determines the mechanism preference. In the III-IV-III mechanism, the outermost ion in the pore is pushed out by a new ion coming from the intracellular fluid, and four-ion states were transiently observed. In the III-II-III mechanism, the outermost ion is pulled out first, without pushing by incoming ions. Increases in the ion concentration and voltage accelerated ion conductions, but their mechanisms were different. The increase in the ion concentrations facilitated the III-IV-III conductions, while the higher voltages increased the III-II-III conductions, indicating that the pore domain of potassium channels permeates ions by using two different driving forces: a push by intracellular ions and a pull by voltage.
authors.affiliation: Graduate School of Information Sciences, Tohoku University, 6-3-09, Aramaki-aza Aoba, Aoba-ku, Sendai, Miyagi 980-8597, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Kasahara
authors.affiliation: Graduate School of Information Sciences, Tohoku University, 6-3-09, Aramaki-aza Aoba, Aoba-ku, Sendai, Miyagi 980-8597, Japan.|Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8573, Japan.|Graduate School of Medicine, Tohoku University, 2-1, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Matsuyuki
authors.initials: M
authors.lastname: Shirota
authors.affiliation: Graduate School of Information Sciences, Tohoku University, 6-3-09, Aramaki-aza Aoba, Aoba-ku, Sendai, Miyagi 980-8597, Japan.|Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8573, Japan.|Institute of Development, Aging, and Cancer, Tohoku University, 4-1, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D001665:Binding Sites; D004553:Electric Conductivity; D051663:Kv1.2 Potassium Channel / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D051663:Kv1.2 Potassium Channel