Syntaxin 1A regulation of weakly inactivating N-type Ca2+ channels

Joyce Hurley, Anne L. Cahill, Meijing Wang, Aaron P. Fox

Research output: Contribution to journalArticle

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Abstract

N- aud P/Q-type Ca2+ channels are abundant in nerve terminals where they interact with proteins of the release apparatus, including syntaxin 1A and SNAP-25. In previous studies on N- or P/Q-type Ca2+ channels, syntaxin 1A co-expression reduced current amplitudes, increased voltage-dependent inactivation and/or enhanced G-protein inhibition. However, these studies were conducted in Ca2+ channels that exhibited significant voltage-dependent inactivation. We previously reported that N-type current in bovine chromaffin cells exhibits very little voltage-dependent inactivation and we identified the Ca2+ channel subunits involved. This study was undertaken to determine the effect of syntaxin 1A on this weakly inactivating Ca2+ channel. Co-expression of syntaxin 1A with the weakly inactivating bovine N-type Ca2+ channels in Xenopus oocytes did not appear to alter inactivation but dramatically reduced current amplitudes, without changing cell surface expression. To further understand the mechanisms of syntaxin 1A regulation of this weakly inactivating channel, we examined mutants of the α 1B subunit, β2a subunit and syntaxin 1A. We determined that the synprint site of α1B and the C-terminal third of syntaxin 1A were necessary for the reduced current amplitude. In addition we show that enhanced G-protein-dependent modulation of the Ca2+ current by syntaxin 1A cannot explain the large suppression of Ca2+ current observed. Of most significance, syntaxin 1A increased voltage-dependent inactivation in channels containing mutant β2a subunits that cannot be palmitoylated. Our data suggest that changes in inactivation can not explain the reduction in current amplitude produced by co-expressing syntaxin and a weakly inactivating Ca2+ channel.

Original languageEnglish
Pages (from-to)351-363
Number of pages13
JournalJournal of Physiology
Volume560
Issue number2
DOIs
StatePublished - Oct 15 2004

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Syntaxin 1
GTP-Binding Proteins
Qa-SNARE Proteins
Chromaffin Cells
Xenopus
Oocytes

ASJC Scopus subject areas

  • Physiology

Cite this

Syntaxin 1A regulation of weakly inactivating N-type Ca2+ channels. / Hurley, Joyce; Cahill, Anne L.; Wang, Meijing; Fox, Aaron P.

In: Journal of Physiology, Vol. 560, No. 2, 15.10.2004, p. 351-363.

Research output: Contribution to journalArticle

Hurley, Joyce ; Cahill, Anne L. ; Wang, Meijing ; Fox, Aaron P. / Syntaxin 1A regulation of weakly inactivating N-type Ca2+ channels. In: Journal of Physiology. 2004 ; Vol. 560, No. 2. pp. 351-363.
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