Energetics of ion conduction through the K+ channel

Nature. 2001 Nov 1;414(6859):73-7. doi: 10.1038/35102067.


K+ channels are transmembrane proteins that are essential for the transmission of nerve impulses. The ability of these proteins to conduct K+ ions at levels near the limit of diffusion is traditionally described in terms of concerted mechanisms in which ion-channel attraction and ion-ion repulsion have compensating effects, as several ions are moving simultaneously in single file through the narrow pore. The efficiency of such a mechanism, however, relies on a delicate energy balance-the strong ion-channel attraction must be perfectly counterbalanced by the electrostatic ion-ion repulsion. To elucidate the mechanism of ion conduction at the atomic level, we performed molecular dynamics free energy simulations on the basis of the X-ray structure of the KcsA K+ channel. Here we find that ion conduction involves transitions between two main states, with two and three K+ ions occupying the selectivity filter, respectively; this process is reminiscent of the 'knock-on' mechanism proposed by Hodgkin and Keynes in 1955. The largest free energy barrier is on the order of 2-3 kcal mol-1, implying that the process of ion conduction is limited by diffusion. Ion-ion repulsion, although essential for rapid conduction, is shown to act only at very short distances. The calculations show also that the rapidly conducting pore is selective.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins*
  • Crystallography, X-Ray
  • Diffusion
  • Energy Metabolism
  • Ion Transport*
  • Models, Molecular
  • Potassium / chemistry
  • Potassium / metabolism*
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Protein Conformation
  • Thermodynamics


  • Bacterial Proteins
  • Potassium Channels
  • prokaryotic potassium channel
  • Potassium