Dynamic rearrangement of the outer mouth of a K+ channel during gating

Neuron. 1996 Apr;16(4):859-67. doi: 10.1016/s0896-6273(00)80106-3.


With prolonged stimulation, voltage-activated K+ channels close by a gating process called inactivation. This inactivation gating can occur by two distinct molecular mechanisms: N-type, in which a tethered particle blocks the intracellular mouth of the pore, and C-type, which involves a closure of the external mouth. The functional motion involved in C-type inactivation was studied by introducing cysteine residues at the outer mouth of Shaker K+ channels through mutagenesis, and by measuring state-dependent changes in accessibility to chemical modification. Modification of three adjacent residues in the outer mouth was 130-10,000-fold faster in the C-type inactivated state than in the closed state. At one position, state-dependent bridging or crosslinking between subunits was also possible. These results give a consistent picture in which C-type inactivation promotes a local rearrangement and constriction of the channel at the outer mouth.

Publication types

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

MeSH terms

  • Cell Line
  • Cross-Linking Reagents
  • Cysteine / chemistry
  • Dithiothreitol / pharmacology
  • Electric Conductivity
  • Embryo, Mammalian
  • Humans
  • Ion Channel Gating / physiology*
  • Kidney
  • Macromolecular Substances
  • Membrane Potentials
  • Methyl Methanesulfonate / pharmacology
  • Mutagenesis, Site-Directed
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Protein Conformation
  • Structure-Activity Relationship
  • Transfection


  • Cross-Linking Reagents
  • Macromolecular Substances
  • Potassium Channels
  • Methyl Methanesulfonate
  • Cysteine
  • Dithiothreitol