The activation gate of a voltage-gated K+ channel can be trapped in the open state by an intersubunit metal bridge

Neuron. 1998 Sep;21(3):617-21. doi: 10.1016/s0896-6273(00)80571-1.


Voltage-activated K+ channels are integral membrane proteins containing a potassium-selective transmembrane pore gated by changes in the membrane potential. This activation gating (opening) occurs in milliseconds and involves a gate at the cytoplasmic side of the pore. We found that substituting cysteine at a particular position in the last transmembrane region (S6) of the homotetrameric Shaker K+ channel creates metal binding sites at which Cd2+ ions can bind with high affinity. The bound Cd2+ ions form a bridge between the introduced cysteine in one channel subunit and a native histidine in another subunit, and the bridge traps the gate in the open state. These results suggest that gating involves a rearrangement of the intersubunit contacts at the intracellular end of S6. The recently solved structure of a bacterial K+ channel shows that the S6 homologs cross in a bundle, leaving an aperture at the bundle crossing. In the context of this structure, the metal ions form a bridge between a cysteine above the bundle crossing and a histidine below the bundle crossing in a neighboring subunit. Our results suggest that gating occurs at the bundle crossing, possibly through a change in the conformation of the bundle itself.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Binding Sites
  • Cadmium / metabolism*
  • Cadmium / pharmacology
  • Cell Line
  • Humans
  • Ion Channel Gating / physiology*
  • Kinetics
  • Macromolecular Substances
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Potassium Channels / chemistry
  • Potassium Channels / physiology*
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Shaker Superfamily of Potassium Channels
  • Transfection


  • Macromolecular Substances
  • Potassium Channels
  • Recombinant Proteins
  • Shaker Superfamily of Potassium Channels
  • Cadmium