Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels

Neuron. 1999 Mar;22(3):549-58. doi: 10.1016/s0896-6273(00)80709-6.


Elevated intracellular Ca2+ triggers inactivation of L-type calcium channels, providing negative Ca2+ feedback in many cells. Ca2+ binding to the main alpha1c channel subunit has been widely proposed to initiate such Ca2+ -dependent inactivation. Here, we find that overexpression of mutant, Ca2+ -insensitive calmodulin (CaM) ablates Ca2+ -dependent inactivation in a "dominant-negative" manner. This result demonstrates that CaM is the actual Ca2+ sensor for inactivation and suggests that CaM is constitutively tethered to the channel complex. Inactivation is likely to occur via Ca2+ -dependent interaction of tethered CaM with an IQ-like motif on the carboxyl tail of alpha1c. CaM also binds to analogous IQ regions of N-, P/Q-, and R-type calcium channels, suggesting that CaM-mediated effects may be widespread in the calcium channel family.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / physiology*
  • Calcium Channels / metabolism
  • Calcium Channels / physiology*
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type*
  • Calcium Signaling / physiology*
  • Calmodulin / biosynthesis
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Calmodulin / physiology*
  • Cloning, Molecular
  • Electrophoresis, Polyacrylamide Gel
  • Feedback / physiology
  • Membrane Potentials
  • Molecular Sequence Data
  • Mutation
  • Patch-Clamp Techniques
  • Rats


  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Calmodulin
  • voltage-dependent calcium channel (P-Q type)
  • Calcium