Unified mechanisms of Ca2+ regulation across the Ca2+ channel family

Neuron. 2003 Sep 11;39(6):951-60. doi: 10.1016/s0896-6273(03)00560-9.


L-type (CaV1.2) and P/Q-type (CaV2.1) calcium channels possess lobe-specific CaM regulation, where Ca2+ binding to one or the other lobe of CaM triggers regulation, even with inverted polarity of modulation between channels. Other major members of the CaV1-2 channel family, R-type (CaV2.3) and N-type (CaV2.2), have appeared to lack such CaM regulation. We report here that R- and N-type channels undergo Ca(2+)-dependent inactivation, which is mediated by the CaM N-terminal lobe and present only with mild Ca2+ buffering (0.5 mM EGTA) characteristic of many neurons. These features, together with the CaM regulatory profiles of L- and P/Q-type channels, are consistent with a simplifying principle for CaM signal detection in CaV1-2 channels-independent of channel context, the N- and C-terminal lobes of CaM appear invariably specialized for decoding local versus global Ca2+ activity, respectively.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / chemistry
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, N-Type / chemistry
  • Calcium Channels, N-Type / genetics
  • Calcium Channels, N-Type / metabolism
  • Calcium Channels, P-Type / chemistry
  • Calcium Channels, P-Type / genetics
  • Calcium Channels, P-Type / metabolism
  • Calcium Channels, Q-Type / chemistry
  • Calcium Channels, Q-Type / genetics
  • Calcium Channels, Q-Type / metabolism
  • Calcium Channels, R-Type / chemistry
  • Calcium Channels, R-Type / genetics
  • Calcium Channels, R-Type / metabolism
  • Calmodulin / metabolism*
  • Cattle
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Sequence Data
  • Rats
  • Sequence Homology, Amino Acid


  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • Calcium Channels, R-Type
  • Calmodulin
  • Calcium