Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel

Nature. 2011 Dec 4;481(7379):94-7. doi: 10.1038/nature10670.


High-conductance voltage- and Ca(2+)-activated K(+) channels function in many physiological processes that link cell membrane voltage and intracellular Ca(2+) concentration, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning. Like other voltage-dependent K(+) channels, Ca(2+)-activated K(+) channels open when the cell membrane depolarizes, but in contrast to other voltage-dependent K(+) channels, they also open when intracellular Ca(2+) concentrations rise. Channel opening by Ca(2+) is made possible by a structure called the gating ring, which is located in the cytoplasm. Recent structural studies have defined the Ca(2+)-free, closed, conformation of the gating ring, but the Ca(2+)-bound, open, conformation is not yet known. Here we present the Ca(2+)-bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca(2+), opens like the petals of a flower. The degree to which it opens explains how Ca(2+) binding can open the transmembrane pore. These findings present a molecular basis for Ca(2+) activation of K(+) channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / metabolism
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cytoplasm / metabolism
  • Electric Conductivity*
  • Humans
  • Hypertension / metabolism
  • Ion Channel Gating* / drug effects
  • Large-Conductance Calcium-Activated Potassium Channels / chemistry*
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Models, Biological
  • Models, Molecular
  • Pliability
  • Protein Structure, Tertiary
  • Zebrafish


  • Large-Conductance Calcium-Activated Potassium Channels
  • Calcium

Associated data

  • PDB/3U6N