Identification of the components controlling inactivation of voltage-gated Ca2+ channels

Neuron. 2004 Mar 4;41(5):745-54. doi: 10.1016/s0896-6273(04)00081-9.


Ca(2+)-dependent inactivation (CDI) of L-type voltage-gated Ca(2+) channels limits Ca(2+) entry into neurons, thereby regulating numerous cellular events. Here we present the isolation and purification of the Ca(2+)-sensor complex, consisting of calmodulin (CaM) and part of the channel's pore-forming alpha(1C) subunit, and demonstrate the Ca(2+)-dependent conformational shift that underlies inactivation. Dominant-negative CaM mutants that prevent CDI block the sensor's Ca(2+)-dependent conformational change. We show how Ile1654 in the CaM binding IQ motif of alpha(1C) forms the link between the Ca(2+) sensor and the downstream inactivation machinery, using the alpha(1C) EF hand motif as a signal transducer to activate the putative pore-occluder, the alpha(1C) I-II intracellular linker.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites / physiology
  • Calcium Channel Blockers / metabolism*
  • Calcium Channels / chemistry
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology
  • Calmodulin / chemistry
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Cattle
  • Female
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Tertiary / genetics
  • Rats
  • Xenopus


  • Calcium Channel Blockers
  • Calcium Channels
  • Calmodulin