Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1

Nat Neurosci. 2002 Mar;5(3):210-7. doi: 10.1038/nn805.


Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.

Publication types

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

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism*
  • Calcium / metabolism
  • Calcium Channels, N-Type / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Calmodulin / metabolism*
  • Cell Line
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Male
  • Models, Molecular
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Subunits
  • Protozoan Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Two-Hybrid System Techniques


  • Calcium Channels, N-Type
  • Calcium-Binding Proteins
  • Calmodulin
  • Chelating Agents
  • Protein Subunits
  • Protozoan Proteins
  • calcium-binding protein 1, Dictyostelium discoideum
  • voltage-dependent calcium channel (P-Q type)
  • Egtazic Acid
  • Calcium