Dissection of functional domains of the voltage-dependent Ca2+ channel α2δ subunit

Ricardo Felix, Christina A. Gurnett, Michel De Waard, Kevin P. Campbell

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Coexpression of the cloned voltage-dependent Ca2+ channel α2δ subunit with the pore-forming α1 subunit results in a significant increase in macroscopic current amplitude. To gain insight into the mechanism underlying this interaction, we have examined the regulatory effect of either the α2δ complex or the δ subunit on the Ca2+ channel α1 subunit. Transient transfection of tsA201 cells with the cardiac L-type α(1c) subunit alone resulted in the expression of inward voltage-activated currents as well as measurable [3H]-PN200-110 binding to membranes from transfected cells. Coexpression of the α2δ subunit significantly increased the macroscopic current amplitude, altered the voltage dependence and the kinetics of the current, and enhanced [3H]-PN200-110 binding. Except for the increase in amplitude, coexpression of the δ subunit reproduced entirely the effects of the full-length α2δ subunit on the biophysical properties of the α(1c) currents. However, no effect on specific [3H]-PN200-110 binding was observed on δ subunit coexpression. Likewise, profound effects on current kinetics of the neuronal α(1A) subunit were observed on coexpression of the α2δ complex in Xenopus oocytes. Furthermore, by using a chimeric strategy, we localized the region involved in this regulation to the transmembrane domain of the δ subunit. These data strongly suggest that the molecular determinants involved in α2δ regulation are conserved across L-type and non-L type Ca2+ channels. Taken together, our results indicate that the region of the α2δ subunit involved in the modulation of the gating properties of the high voltage-activated calcium channels is localized in the δ domain of the protein. In contrast, the level of membrane expression of functional channels relies on the presence of the α2 domain of the α2δ complex.

Original languageEnglish
Pages (from-to)6884-6891
Number of pages8
JournalJournal of Neuroscience
Volume17
Issue number18
DOIs
StatePublished - 1997

Keywords

  • Dihydropyridine binding
  • L-type Ca channel
  • P/Q-type Ca channels
  • Transient expression
  • tsA201 cells
  • αδ subunit
  • δ subunit

Fingerprint

Dive into the research topics of 'Dissection of functional domains of the voltage-dependent Ca2+ channel α2δ subunit'. Together they form a unique fingerprint.

Cite this