Ion concentration-dependent ion conduction mechanism of a voltage-sensitive potassium channel

PLoS One. 2013;8(2):e56342. doi: 10.1371/journal.pone.0056342. Epub 2013 Feb 13.


Voltage-sensitive potassium ion channels are essential for life, but the molecular basis of their ion conduction is not well understood. In particular, the impact of ion concentration on ion conduction has not been fully studied. We performed several micro-second molecular dynamics simulations of the pore domain of the Kv1.2 potassium channel in KCl solution at four different ion concentrations, and scrutinized each of the conduction events, based on graphical representations of the simulation trajectories. As a result, we observed that the conduction mechanism switched with different ion concentrations: at high ion concentrations, potassium conduction occurred by Hodgkin and Keynes' knock-on mechanism, where the association of an incoming ion with the channel is tightly coupled with the dissociation of an outgoing ion, in a one-step manner. On the other hand, at low ion concentrations, ions mainly permeated by a two-step association/dissociation mechanism, in which the association and dissociation of ions were not coupled, and occurred in two distinct steps. We also found that this switch was triggered by the facilitated association of an ion from the intracellular side within the channel pore and by the delayed dissociation of the outermost ion, as the ion concentration increased.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ion Transport / drug effects
  • Ions / chemistry
  • Ions / metabolism*
  • Ions / pharmacology
  • Kv1.2 Potassium Channel / chemistry
  • Kv1.2 Potassium Channel / metabolism
  • Models, Biological*
  • Models, Chemical
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Potassium / chemistry
  • Potassium / metabolism
  • Potassium / pharmacology
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Protein Conformation


  • Ions
  • Kv1.2 Potassium Channel
  • Potassium Channels
  • Potassium

Grant support

This work was funded by the “HD-Physiology” Grant-in-Aid for Scientific Research on Innovative Areas (22136005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.