The C terminus of the Ca channel α1B subunit mediates selective inhibition by G-protein-coupled receptors

Arthur A. Simen, Chong C. Lee, Birgitte B. Simen, Vytautas P. Bindokas, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Inhibition of calcium channels by G-protein-coupled receptors depends on the nature of the Gα subunit, although the Gβγ complex is thought to be responsible for channel inhibition. Ca currents in hypothalamic neurons and N-type calcium channels expressed in HEK-293 cells showed robust inhibition by Gi/Go-coupled galanin receptors (GalR1), but not by Gq-coupled galanin receptors (GalR2). However, deletions in the C terminus of α1B-1 produced Ca channels that were inhibited after activation of both GalR1 and GalR2. Inhibition of protein kinase C (PKC) also revealed Ca current modulation by GalR2. Imaging studies using green fluorescent protein fusions of the C terminus of α1B demonstrated that activation of the GalR2 receptor caused translocation of the C terminus of α1B-1 to the membrane and co-localization with Gαq and PKC. Similar translocation was not seen with a C-terminal truncated splice variant, α1B-2. Immunoprecipitation experiments demonstrated that Gαq interacts directly with the C terminus of the α1B subunit. These results are consistent with a model in which local activation of PKC by channel-associated Gαq blocks modulation of the channel by Gβγ released by Gq-coupled receptors.

Original languageEnglish (US)
Pages (from-to)7587-7597
Number of pages11
JournalJournal of Neuroscience
Volume21
Issue number19
StatePublished - Oct 1 2001

Keywords

  • C terminus
  • Ca channels
  • G-protein receptors
  • G-proteins
  • Galanin
  • Gαq
  • PKC

ASJC Scopus subject areas

  • Neuroscience(all)

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