CaBP1 regulates voltage-dependent inactivation and activation of Ca(V)1.2 (L-type) calcium channels

J Biol Chem. 2011 Apr 22;286(16):13945-53. doi: 10.1074/jbc.M110.198424. Epub 2011 Mar 7.


CaBP1 is a Ca(2+)-binding protein that regulates the gating of voltage-gated (Ca(V)) Ca(2+) channels. In the Ca(V)1.2 channel α(1)-subunit (α(1C)), CaBP1 interacts with cytosolic N- and C-terminal domains and blunts Ca(2+)-dependent inactivation. To clarify the role of the α(1C) N-terminal domain in CaBP1 regulation, we compared the effects of CaBP1 on two alternatively spliced variants of α(1C) containing a long or short N-terminal domain. In both isoforms, CaBP1 inhibited Ca(2+)-dependent inactivation but also caused a depolarizing shift in voltage-dependent activation and enhanced voltage-dependent inactivation (VDI). In binding assays, CaBP1 interacted with the distal third of the N-terminal domain in a Ca(2+)-independent manner. This segment is distinct from the previously identified calmodulin-binding site in the N terminus. However, deletion of a segment in the proximal N-terminal domain of both α(1C) isoforms, which spared the CaBP1-binding site, inhibited the effect of CaBP1 on VDI. This result suggests a modular organization of the α(1C) N-terminal domain, with separate determinants for CaBP1 binding and transduction of the effect on VDI. Our findings expand the diversity and mechanisms of Ca(V) channel regulation by CaBP1 and define a novel modulatory function for the initial segment of the N terminus of α(1C).

Publication types

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

MeSH terms

  • Alternative Splicing
  • Animals
  • Binding Sites
  • Calcium / chemistry
  • Calcium Channels / chemistry
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Calmodulin / chemistry
  • Female
  • Gene Deletion
  • Humans
  • Kinetics
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Xenopus


  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium-Binding Proteins
  • Calmodulin
  • L-type calcium channel alpha(1C)
  • Protein Isoforms
  • Ca2+-binding protein-1
  • Calcium