Ca2+/calmodulin binds to and modulates P/Q-type calcium channels

Nature. 1999 May 13;399(6732):155-9. doi: 10.1038/20194.


Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Channels, N-Type*
  • Calmodulin / metabolism*
  • Cell Line
  • Chelating Agents
  • Cloning, Molecular
  • Egtazic Acid
  • Molecular Sequence Data
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Yeasts


  • Calcium Channels
  • Calcium Channels, N-Type
  • Calmodulin
  • Chelating Agents
  • Recombinant Fusion Proteins
  • voltage-dependent calcium channel (P-Q type)
  • Egtazic Acid
  • Calcium