Structural features determining differential receptor regulation of neuronal Ca channels

Arthur A. Simen, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Dihydropyridine-insensitive Ca channels are subject to direct receptor G-protein-mediated inhibition to differing extents. α(1B) channels are much more strongly modulated than α(1E) channels. To understand the structural basis for this difference, we have constructed and expressed various α(1B) and α(1E) chimeric Ca channels and examined their regulation by κ-opioid receptors. Replacement of the first membrane-spanning domain of α(1E) with the corresponding region of α(1B) resulted in a chimeric Ca channel that was modulated by κ-opioid receptors to a significantly greater extent than α(1E). Transfer of the N terminus and I/II loop from α(1B) in addition to domain I resulted in a chimeric channel that was modulated to the same extent as α(1B). Other regions of the molecule do not appear to contribute significantly to the degree of inhibition obtained, although the C terminus may contribute to facilitation.

Original languageEnglish (US)
Pages (from-to)3689-3698
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number10
DOIs
StatePublished - May 15 1998

Keywords

  • Calcium channels
  • G-proteins
  • Inverse agonism
  • Modulation
  • Opioid receptors
  • Structure- function

ASJC Scopus subject areas

  • Neuroscience(all)

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