QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (30) Citing Articles via Google Scholar Google Scholar Articles by Bergsman, J. B. Articles by Tsien, R. W. Search for Related Content PubMed PubMed Citation Articles by Bergsman, J. B. Articles by Tsien, R. W. Pubmed/NCBI databases Substance via MeSH

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 15, 2000, 20(12):4368-4378

Syntaxin Modulation of Calcium Channels in Cortical Synaptosomes As Revealed by Botulinum Toxin C1

Jeremy B. Bergsman^{1, 2} and Richard W. Tsien²

¹ Neurosciences Program, and ² Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine, Stanford, California 94305

When the presynaptic membrane protein syntaxin is coexpressed in Xenopus oocytes with N- or P/Q-type Ca²⁺ channels, it promotes their inactivation (Bezprozvanny et al., 1995; Wiser et al., 1996, 1999; Degtiar et al., 2000) (I. B. Bezprozvanny, P. Zhong, R. H. Scheller, and R. W. Tsien, unpublished observations). These findings led to the hypothesis that syntaxin influences Ca²⁺ channel function in presynaptic endings, in a reversal of the conventional flow of information from Ca²⁺ channels to the release machinery. We examined this effect in isolated mammalian nerve terminals (synaptosomes). Botulinum neurotoxin type C1 (BoNtC1), which cleaves syntaxin, was applied to rat neocortical synaptosomes at concentrations that completely blocked neurotransmitter release. This treatment altered the pattern of Ca²⁺ entry monitored with fura-2. Whereas the initial Ca²⁺ rise induced by depolarization with K⁺-rich solution was unchanged, late Ca²⁺ entry was strongly augmented by syntaxin cleavage. Similar results were obtained when Ca²⁺ influx arose from repetitive firing induced by the K⁺-channel blocker 4-aminopyridine. Cleavage of vesicle-associated membrane protein with BoNtD or SNAP-25 with BoNtE failed to produce a significant change in Ca²⁺ entry. The BoNtC1-induced alteration in Ca²⁺ signaling was specific to voltage-gated Ca²⁺ channels, not Ca²⁺ extrusion or buffering, and it involved N-, P/Q- and R-type channels, the high voltage-activated channels most intimately associated with presynaptic release machinery. The modulatory effect of syntaxin was not immediately manifest when synaptosomes had been K⁺-predepolarized in the absence of external Ca²⁺, but developed with a delay after admission of Ca²⁺, suggesting that vesicular turnover may be necessary to make syntaxin available for its stabilizing effect on Ca²⁺ channel inactivation.

Key words: synaptosome; syntaxin; calcium channel; SNARE; synapse; synaptic vesicle; modulation; clostridium botulinum; toxin; neurotoxin; conotoxin; agatoxin; rat

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20124368-11$05.00/0

This article has been cited by other articles:

				C. G. Phillips, M. T. Harnett, W. Chen, and S. M. Smith Calcium-Sensing Receptor Activation Depresses Synaptic Transmission J. Neurosci., November 12, 2008; 28(46): 12062 - 12070. [Abstract] [Full Text] [PDF]

				R. A. Nichols, A. F. Dengler, E. M. Nakagawa, M. Bashkin, B. T. Paul, J. Wu, and G. M. Khan A Constitutive, Transient Receptor Potential-like Ca2+ Influx Pathway in Presynaptic Nerve Endings Independent of Voltage-gated Ca2+ Channels and Na+/Ca2+ Exchange J. Biol. Chem., December 7, 2007; 282(49): 36102 - 36111. [Abstract] [Full Text] [PDF]

				R. R. Llinas, S. Choi, F. J. Urbano, and H.-S. Shin {gamma}-Band deficiency and abnormal thalamocortical activity in P/Q-type channel mutant mice PNAS, November 6, 2007; 104(45): 17819 - 17824. [Abstract] [Full Text] [PDF]

				R. K. Keith, R. E. Poage, C. T. Yokoyama, W. A. Catterall, and S. D. Meriney Bidirectional Modulation of Transmitter Release by Calcium Channel/Syntaxin Interactions In Vivo J. Neurosci., January 10, 2007; 27(2): 265 - 269. [Abstract] [Full Text] [PDF]

				H. W. Tedford and G. W. Zamponi Direct G Protein Modulation of Cav2 Calcium Channels Pharmacol. Rev., December 1, 2006; 58(4): 837 - 862. [Abstract] [Full Text] [PDF]

				M. K. Sandberg and P. Low Altered Interaction and Expression of Proteins Involved in Neurosecretion in Scrapie-infected GT1-1 Cells J. Biol. Chem., January 14, 2005; 280(2): 1264 - 1271. [Abstract] [Full Text] [PDF]

				S. E. Gladycheva, C. S. Ho, Y. Y. F. Lee, and E. L. Stuenkel Regulation of syntaxin1A-munc18 complex for SNARE pairing in HEK293 cells J. Physiol., August 1, 2004; 558(3): 857 - 871. [Abstract] [Full Text] [PDF]

				Q. Li, A. Lau, T. J. Morris, L. Guo, C. B. Fordyce, and E. F. Stanley A Syntaxin 1, G{alpha}o, and N-Type Calcium Channel Complex at a Presynaptic Nerve Terminal: Analysis by Quantitative Immunocolocalization J. Neurosci., April 21, 2004; 24(16): 4070 - 4081. [Abstract] [Full Text] [PDF]

				G. W. Zamponi and T. P. Snutch Modulating Modulation: Crosstalk Between Regulatory Pathways of Presynaptic Calcium Channels Mol. Interv., December 1, 2002; 2(8): 476 - 478. [Abstract] [Full Text]

				I. Michaelevski, D. Chikvashvili, S. Tsuk, O. Fili, M. J. Lohse, D. Singer-Lahat, and I. Lotan Modulation of a Brain Voltage-gated K+ Channel by Syntaxin 1A Requires the Physical Interaction of Gbeta gamma with the Channel J. Biol. Chem., September 13, 2002; 277(38): 34909 - 34917. [Abstract] [Full Text] [PDF]

				T. Fergestad, M. N. Wu, K. L. Schulze, T. E. Lloyd, H. J. Bellen, and K. Broadie Targeted Mutations in the Syntaxin H3 Domain Specifically Disrupt SNARE Complex Function in Synaptic Transmission J. Neurosci., December 1, 2001; 21(23): 9142 - 9150. [Abstract] [Full Text] [PDF]

				O. Fili, I. Michaelevski, Y. Bledi, D. Chikvashvili, D. Singer-Lahat, H. Boshwitz, M. Linial, and I. Lotan Direct Interaction of a Brain Voltage-Gated K+ Channel with Syntaxin 1A: Functional Impact on Channel Gating J. Neurosci., March 15, 2001; 21(6): 1964 - 1974. [Abstract] [Full Text] [PDF]

				I. Bezprozvanny, P. Zhong, R. H. Scheller, and R. W. Tsien Molecular determinants of the functional interaction between syntaxin and N-type Ca2+ channel gating PNAS, November 16, 2000; (2000) 220389697. [Abstract] [Full Text]

				V. E. Degtiar, R. H. Scheller, and R. W. Tsien Syntaxin Modulation of Slow Inactivation of N-Type Calcium Channels J. Neurosci., June 15, 2000; 20(12): 4355 - 4367. [Abstract] [Full Text] [PDF]

				I. Bezprozvanny, P. Zhong, R. H. Scheller, and R. W. Tsien Molecular determinants of the functional interaction between syntaxin and N-type Ca2+ channel gating PNAS, December 5, 2000; 97(25): 13943 - 13948. [Abstract] [Full Text] [PDF]

				B. A. Stewart, M. Mohtashami, W. S. Trimble, and G. L. Boulianne SNARE proteins contribute to calcium cooperativity of synaptic transmission PNAS, December 5, 2000; 97(25): 13955 - 13960. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help