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.
Highlights
Ion channels are an essential class of proteins that function to transport ions across a plasma membrane [1]
As in Jensen’s study [26], our molecular dynamics (MD) simulations underestimated the ion currents, especially in the low voltage regime. This underestimation may be due to the insufficiencies of the force field to reproduce accurate interactions of the selectivity filter and ions, or due to the other factors that were not treated in this study, e.g., complex mixture of membrane components in the physiological conditions
We previously reported the dependency of the ion conduction mechanisms on the ion concentration, and concluded that high ion concentrations tend to facilitate the III-IV-III conduction, due to an increase in the frequency of ions approaching the pore entrance [28]
Summary
Ion channels are an essential class of proteins that function to transport ions across a plasma membrane [1]. In particular, play a central role in several high-order physiological phenomena, such as establishing action potentials in heart muscles [2]. They passively transport K+ ions with high selectivity from other monovalent cations [3,4,5]. One of the important characteristics of potassium channels is their precise control of ion conductance. PLOS ONE | DOI:10.1371/journal.pone.0150716 March 7, 2016
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