• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jphysiolThe Journal of Physiology SiteMembershipSubmissionJ Physiol
J Physiol. Oct 15, 1997; 504(Pt 2): 251–258.
PMCID: PMC1159907

Voltage-dependent interaction between the muscarinic ACh receptor and proteins of the exocytic machinery.


1. Release of neurotransmitter into the synaptic cleft is the last step in the chain of molecular events following the arrival of an action potential at the nerve terminal. The neurotransmitter exerts negative feedback on its own release. This inhibition would be most effective if exerted on the first step in this chain of events, i.e. a step that is mediated by membrane depolarization. Indeed, in numerous studies feedback inhibition was found to be voltage dependent. 2. The purpose of this study is to investigate whether the mechanism underlying feedback inhibition of transmitter release resides in interaction between the presynaptic autoreceptors and the exocytic apparatus, specifically the soluble NSF-attachment protein receptor (SNARE) complex. 3. Using rat synaptosomes we show that the muscarinic ACh autoreceptor (mAChR) is an integral component of the exocytic machinery. It interacts with syntaxin, synaptosomal-associated protein of 25 kDa (SNAP-25), vesicle-associated membrane protein (VAMP) and synaptotagmin as shown using both cross-linking and immunoprecipitation. 4. The interaction between mAChRs and both syntaxin and SNAP-25 is modulated by depolarization levels; binding is maximal at resting potential and disassembly occurs at higher depolarization. 5. This voltage-dependent interaction of mAChRs with the secretory core complex appears suitable for controlling the rapid, synchronous neurotransmitter release at nerve terminals.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Augustine GJ, Charlton MP, Smith SJ. Calcium action in synaptic transmitter release. Annu Rev Neurosci. 1987;10:633–693. [PubMed]
  • Bennett MK. SNAREs and the specificity of transport vesicle targeting. Curr Opin Cell Biol. 1995 Aug;7(4):581–586. [PubMed]
  • Bennett MK, Scheller RH. A molecular description of synaptic vesicle membrane trafficking. Annu Rev Biochem. 1994;63:63–100. [PubMed]
  • Bezprozvanny I, Scheller RH, Tsien RW. Functional impact of syntaxin on gating of N-type and Q-type calcium channels. Nature. 1995 Dec 7;378(6557):623–626. [PubMed]
  • Dolezal V, Tucek S. Presynaptic muscarinic receptors and the release of acetylcholine from cerebrocortical prisms: roles of Ca2+ and K+ concentrations. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):228–233. [PubMed]
  • Keith RA, Horn MB, Piser TM, Mangano TJ. Effects of stimulus intensity on the inhibition by omega-conotoxin GVIA and neomycin of K(+_-evoked [3H]norepinephrine release from hippocampal brain slices and synaptosomal calcium influx. Biochem Pharmacol. 1993 Jan 7;45(1):165–171. [PubMed]
  • Kloog Y, Michaelson DM, Sokolovsky M. Characterization of the presynaptic muscarinic receptor in synaptosomes of Torpedo electric organ by means of kinetic and equilibrium binding studies. Brain Res. 1980 Jul 21;194(1):97–115. [PubMed]
  • Linial M, Levius O, Ilouz N, Parnas D. The effect of calcium levels on synaptic proteins. A study on VAT-1 from Torpedo. J Physiol Paris. 1995;89(2):103–112. [PubMed]
  • Linial M, Parnas D. Deciphering neuronal secretion: tools of the trade. Biochim Biophys Acta. 1996 Jun 10;1286(2):117–152. [PubMed]
  • Mochida S, Sheng ZH, Baker C, Kobayashi H, Catterall WA. Inhibition of neurotransmission by peptides containing the synaptic protein interaction site of N-type Ca2+ channels. Neuron. 1996 Oct;17(4):781–788. [PubMed]
  • Parnas H, Parnas I. Neurotransmitter release at fast synapses. J Membr Biol. 1994 Dec;142(3):267–279. [PubMed]
  • Parnas H, Parnas I, Ravin R, Yudelevitch B. Glutamate and N-methyl-D-aspartate affect release from crayfish axon terminals in a voltage-dependent manner. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11586–11590. [PMC free article] [PubMed]
  • Parnas I, Dudel J, Parnas H, Ravin R. Glutamate depresses release by activating non-conventional glutamate receptors at crayfish nerve terminals. Eur J Neurosci. 1996 Jan;8(1):116–126. [PubMed]
  • Sánchez-Prieto J, Budd DC, Herrero I, Vázquez E, Nicholls DG. Presynaptic receptors and the control of glutamate exocytosis. Trends Neurosci. 1996 Jun;19(6):235–239. [PubMed]
  • Sheng ZH, Rettig J, Cook T, Catterall WA. Calcium-dependent interaction of N-type calcium channels with the synaptic core complex. Nature. 1996 Feb 1;379(6564):451–454. [PubMed]
  • Söllner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993 Mar 25;362(6418):318–324. [PubMed]
  • Starke K, Göthert M, Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev. 1989 Jul;69(3):864–989. [PubMed]
  • Südhof TC. The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature. 1995 Jun 22;375(6533):645–653. [PubMed]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...