Molecular driving forces determining potassium channel slow inactivation

Nat Struct Mol Biol. 2007 Nov;14(11):1062-9. doi: 10.1038/nsmb1309. Epub 2007 Oct 7.


K+ channels undergo a time-dependent slow inactivation process that plays a key role in modulating cellular excitability. Here we show that in the prokaryotic proton-gated K+ channel KcsA, the number and strength of hydrogen bonds between residues in the selectivity filter and its adjacent pore helix determine the rate and extent of C-type inactivation. Upon channel activation, the interaction between residues at positions Glu71 and Asp80 promotes filter constriction parallel to the permeation pathway, which affects K+-binding sites and presumably abrogates ion conduction. Coupling between these two positions results in a quantitative correlation between their interaction strength and the stability of the inactivated state. Engineering of these interactions in the eukaryotic voltage-dependent K+ channel Kv1.2 suggests that a similar mechanistic principle applies to other K+ channels. These observations provide a plausible physical framework for understanding C-type inactivation in K+ channels.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Asparagine / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Histidine / metabolism
  • Hydrogen Bonding
  • Ion Channel Gating / physiology*
  • Kv1.2 Potassium Channel / chemistry*
  • Kv1.2 Potassium Channel / genetics
  • Kv1.2 Potassium Channel / metabolism*
  • Liposomes / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Oocytes / cytology
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Protein Conformation*
  • Rats
  • Xenopus laevis


  • Bacterial Proteins
  • Kv1.2 Potassium Channel
  • Liposomes
  • Potassium Channels
  • prokaryotic potassium channel
  • Histidine
  • Asparagine

Associated data

  • PDB/2P7T