Calcium activation of BK(Ca) potassium channels lacking the calcium bowl and RCK domains

Nature. 2002 Dec 5;420(6915):499-502. doi: 10.1038/nature01199.

Abstract

In many physiological systems such as neurotransmitter release, smooth muscle relaxation and frequency tuning of auditory hair cells, large-conductance calcium-activated potassium (BK(Ca)) channels create a connection between calcium signalling pathways and membrane excitability. BK(Ca) channels are activated by voltage and by micromolar concentrations of intracellular calcium. Although it is possible to open BK(Ca) channels in the absence of calcium, calcium binding is essential for their activation under physiological conditions. In the presence of intracellular calcium, BK(Ca) channels open at more negative membrane potentials. Many experiments investigating the molecular mechanism of calcium activation of the BK(Ca) channel have focused on the large intracellular carboxy terminus, and much evidence supports the hypothesis that calcium-binding sites are located in this region of the channel. Here we show that BK(Ca) channels that lack the whole intracellular C terminus retain wild-type calcium sensitivity. These results show that the intracellular C terminus, including the 'calcium bowl' and the RCK domain, is not necessary for the calcium-activated opening of these channels.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Calcium / pharmacology*
  • Cell Line
  • Electric Conductivity
  • Humans
  • Ion Channel Gating / drug effects*
  • Large-Conductance Calcium-Activated Potassium Channels
  • Mice
  • Mutation
  • Oocytes / metabolism
  • Potassium / metabolism
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors
  • Potassium Channels, Calcium-Activated / chemistry*
  • Potassium Channels, Calcium-Activated / genetics
  • Potassium Channels, Calcium-Activated / metabolism*
  • Protein Structure, Tertiary
  • Xenopus laevis

Substances

  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Potassium
  • Calcium