Skip to main content

New Evidence Supporting the Vesicle Hypothesis for Quantal Secretion at the Neuromuscular Junction

  • Conference paper
Cellular and Molecular Basis of Synaptic Transmission

Part of the book series: NATO ASI Series ((ASIH,volume 21))

Abstract

Acetylcholine (ACh) is stored in two compartments within vertebrate motor terminals: the cytoplasm and the synaptic vesicles (Whittaker et al., 1964; Dunant et al., 1972); it is released from terminals in two ways: continuously in a relatively steady molecular stream (Katz and Miledi, 1977; Vyskocil and Illes, 1979), and intermittantly in pulses, or quanta, (Fatt and Katz, 1952, del Castillo and Katz, 1954) which contain about 104 molecules (Kuffler and Yoshikami, 1975). The function of the continuous leak is not understood (Edwards et al., 1985), but the spontaneous or neurally evoked release of quanta generates the discrete, transient miniature endplate potentials (mepps) or endplate potentials (epps) that mediate neuromuscular transmission. Two hypotheses have been proposed for the origin of the quanta: a) the cytoplasmic hypothesis which postulates that quanta are comprised of cytoplasmic ACh which diffuses in pulses through channels in the axolemma which become intermittantly permeable to it (Israel and Manaranche, 1985), and b) the vesicle hypothesis which postulates that quanta are comprised of ACh which is released by exocytosis from the interiors of synaptic vesicles whose membranes have fused with the axolemma (del Castillo and Katz, 1956). In our opinion, the vast preponderance of evidence supports the vesicle hypothesis of quantal secretion, though its proof is not yet absolute and most of the mechanistic details of the fusion and recovery processes have yet to be worked out.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Birks R, Huxley HE and Katz B (1960) The fine structure of the neuromuscular junction of the frog. J Physiol Lond 150: 134–144.

    PubMed  CAS  Google Scholar 

  • Birks RI and Cohen MW (1968) The action of sodium pump inhibitors on neuromuscular transmission. Proc R Soc Lond B 170: 381–399.

    Article  PubMed  CAS  Google Scholar 

  • Breckenridge LJ and Aimers W (1987a) Currents through the fusion pore that forms during exocytosis of a secretory vesicle. Nature 328: 814–817.

    Article  PubMed  CAS  Google Scholar 

  • Breckenridge LJ and Aimers W (1987b) Final steps in exocytosis observed in a cell with giant secretory granules. Proc Natl Acad Sci USA 84: 1945–1949.

    Article  PubMed  CAS  Google Scholar 

  • Campbell N (1909) The study of discontinuous phenomena. Proc Cambridge Phil Soc 15: 117–136.

    Google Scholar 

  • Ceccarelli B, Fesce R, Grohovaz F and Haimann C (1988a) The effect of potassium on exocytosis of transmitter at the frog neuromuscular junction. J Physiol Lond, in press.

    Google Scholar 

  • Ceccarelli B, Grohovaz F and Hurlbut WP (1979a) Freeze-fracture studies of frog neuromuscular junctions during intens release of neurotransmitter. I. Effects of Black Widow Spider Venom and Ca2+ -free solutions on the structure of the active zone. J Cell Biol 81: 163–177.

    Google Scholar 

  • Ceccarelli B, Grohovaz F and Hurlbut WP (1979b) Freeze-fracture studies of frog neuromuscular junctions during intense release of neurotransmitter. II. Effects of electrical stimulation and high potassium. J Cell Biol 81: 178–192.

    Google Scholar 

  • Ceccarelli B and Hurlbut WP (1975) The effects of prolonged repetitive stimulation in hemicholinium on the frog neuromuscular junction. J Physiol Lond 247: 163–188.

    PubMed  CAS  Google Scholar 

  • Ceccarelli B and Hurlbut WP (1980a) Ca -dependent recycling of synaptic vesicles at the frog neuromuscular junction. J Cell Biol 87: 297–303.

    Article  PubMed  CAS  Google Scholar 

  • Ceccarelli B and Hurlbut WP (1980b) Vesicle hypothesis of the release of quanta of acetylcholine. Physiol Rev 60: 396–441.

    PubMed  CAS  Google Scholar 

  • Ceccarelli B, Hurlbut WP and Iezzi N (1988b) Effect of a-latrotoxin on the frog neuromuscular junction at low temperature. J Physiol Lond, submitted.

    Google Scholar 

  • Ceccarelli B, Hurlbut WP and Mauro A (1972) Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation. J Cell Biol 54: 30–38.

    Article  PubMed  CAS  Google Scholar 

  • Ceccarelli B, Hurlbut WP and Mauro A (1973) Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. J Cell Biol 57: 499–524.

    Article  PubMed  CAS  Google Scholar 

  • De Camilli P and Greengard P (1986) Synapsin I: a synaptic vesicle-associated neuronal phosphoprotein. Biochem Pharmacol 35: 4349–4357.

    Article  PubMed  Google Scholar 

  • de Robertis EDP and Bennet HS (1955) Some features of the submicroscopic morphology of synapses in frog and earthworm. J Biophys Biochem Cytol 3: 47–58.

    Article  Google Scholar 

  • del Castillo J and Katz B (1954) Quantal components of the end-plate potential. J Physiol Lond 124: 560–573.

    Google Scholar 

  • del Castillo J and Katz B (1956) Biophysical aspects of neuro-muscular transmission. Prog Biophys Biophys Chem 6: 121–170.

    Google Scholar 

  • Dunant Y, Gautron J, Israel M, Lesbats B and Manaranche R (1972) Les compartiments d’acetylcholine de l’organe electrique de la Torpille et leurs modifications par la stimulation. J Neurochem 19: 1987–2002.

    Article  PubMed  CAS  Google Scholar 

  • Edwards C, Dolezal V, Tucek S, Zemkova H and Vyskocil R (1985) Is an acetylcholine transport system responsible for nonquantal release of acetylcholine at the rodent myoneural junction? Proc Natl Acad Sci USA 82: 3514–3518.

    Article  PubMed  CAS  Google Scholar 

  • Escaig J (1981) New instruments which facilitate rapid freezing at 83 K and 6 K. J Microsc Paris 126: 221–229.

    Article  Google Scholar 

  • Fatt P and Katz B (1952) Spontaneous subthreshold activity at motor nerve endings. J Physiol Lond 117: 109–128.

    PubMed  CAS  Google Scholar 

  • Fesce R, Segal JR, Ceccarelli B and Hurlbut WP (1986a) Effects of Black Widow Spider Venom and Ca2+ on quantal secretion at the frog neuromuscular junction. J Gen Physiol 88: 59–81.

    Article  PubMed  CAS  Google Scholar 

  • Fesce R, Segal JR and Hurlbut WP (1986b) Fluctuation analysis of nonideal shot noise. Application to the neuromuscular junction. J Gen Physiol 88: 25–57.

    Google Scholar 

  • Florey E and Kriebel ME (1983) Changes in acetylcholine concentration, miniature end-plate potentials and synaptic vesicles in frog neuromuscular preparations during lanthanum treatment. Comp Biochem Physiol 75c: 285–294.

    CAS  Google Scholar 

  • Gorio A, Hurlbut WP and Ceccarelli B (1978) Acetylcholine compartments in mouse diaphragm. Comparison of the effects of Black Widow Spider Venom, electrical stimulation, and high concentrations of potassium. J Cell Biol 78: 716–733.

    Google Scholar 

  • Haimann C, Torri-Tarelli F, Fesce R and Ceccarelli B (1985) Measurement of quantal secretion induced by ouabain and its correlation with depletion of synaptic vesicles. J Cell Biol 101: 1953–1965.

    Article  PubMed  CAS  Google Scholar 

  • Heuser JE and Reese TS (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J Cell Biol 57: 315–344.

    Article  PubMed  CAS  Google Scholar 

  • Heuser JE, Reese T, Dennis MJ, Jan Y and Evans L (1979) Synaptic vesicle exocytosis captured by quick-freezing and correlated with quantal transmitter release. J Cell Biol 81: 275–300.

    Article  PubMed  CAS  Google Scholar 

  • Heuser JE, Reese TS and Landis DMD (1974) Functional changes in frog neuromuscular junctions studied with freeze-fracture. J Neurocytol 3: 109–131.

    Article  PubMed  CAS  Google Scholar 

  • Hurlbut WP and Ceccarelli B (1979) Use of Black Widow Spider Venom to study the release of neurotransmitter. In: Ceccarelli B and Clementi F (eds). Advances in Cytopharmacology. Raven Press New York 3: 87–115.

    Google Scholar 

  • Huttner WB, Schiebler W, Greengard P and De Camilli P (1983) Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J Cell Biol 96: 1374–1388.

    Google Scholar 

  • Israel M, Dunant Y and Manaranche R (1979) The present status of the vesicular hypothesis. Progr Neurobiol 13: 237–275.

    Article  CAS  Google Scholar 

  • Israel M and Manaranche R (1985) The release of acetylcholine: from a cellular towards a molecular mechanism. Biol Cell 55: 1–14.

    Article  PubMed  CAS  Google Scholar 

  • Jahn R, Schiebler W, Ouimet C and Greengard P (1985) A 38,000-dalton membrane protein (p38) present in synaptic vesicles. Proc Natl Acad Sci USA 82: 4137–4141.

    Article  PubMed  CAS  Google Scholar 

  • Katz B and Miledi R (1977) Transmitter leakage from motor nerve endings. Proc R Soc Lond B 196: 59–72.

    Article  PubMed  CAS  Google Scholar 

  • Katz B and Miledi R (1979) Estimates of quantal content during “chemical potentiation” of transmitter release. Proc R Soc Lond B 205: 369–378.

    Article  PubMed  CAS  Google Scholar 

  • Kriebel ME and Florey E (1983) Effect of lanthanum ions on the amplitude distribution of miniature endplate potentials and on synaptic vesicles in frog neuromuscular junctions. Neurosci 9: 535–547.

    Article  CAS  Google Scholar 

  • Kriebel ME and Gross CE (1974) Multimodal distribution of frog miniature endplate potentials in adult, denervated and tadpole leg muscle. J Gen Physiol 64: 85–103.

    Article  PubMed  CAS  Google Scholar 

  • Kuffler SW and Yoshikami D (1975) The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. J Physiol Lond 251: 465–482.

    PubMed  CAS  Google Scholar 

  • Lambert DH and Parsons RL (1970) Influence of polyvalent cations on the activation of muscle end plate receptors. J Gen Physiol 56: 309–321.

    Article  PubMed  CAS  Google Scholar 

  • Lasansky A (1980) Lateral contacts and interactions of horizontal cell dendrites in the retina of the larval tiger salamander. J Physiol Lond 301: 59–68.

    PubMed  CAS  Google Scholar 

  • Llinas R, McGuinness TL, Leonard CS, Sugimori M and Greengard P (1985) Intraterminal injection of synapsin I or calcium/calmodulin dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sci USA 82: 3035–3039.

    Article  PubMed  CAS  Google Scholar 

  • Lundh H, Leander S and Thesleff S (1977) Antagonism of the paralysis produced by botulinum toxin in the rat. J Neurol Sci 32: 29–43.

    Article  PubMed  CAS  Google Scholar 

  • Macintosh FC (1980) The role of vesicles in cholinergic systems. In: Brzin M, Sket D and Bachelard H (eds). Synaptic constituents in Health and Disease. Pergamon Press Oxford: 11–52.

    Google Scholar 

  • Marchbanks RM (1979) Role of storage vesicles in synaptic transmission. In: Hopkins and Duncan (eds). Secretory Mechanisms. Soc Exp Biol Symp XXXII: 251–276.

    Google Scholar 

  • Neher E and Marty A (1982) Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc Natl Acad Sci USA 79: 6712–6716.

    Article  PubMed  CAS  Google Scholar 

  • Palade GE (1975) Intracellular aspects of the process of protein synthesis. Science Wash DC 189: 347–358.

    Article  CAS  Google Scholar 

  • Palay SL (1956) Synapses in the central nervous system. J Biophys Biochem Cytol Suppl 2: 193–202.

    Article  CAS  Google Scholar 

  • Reichardt LF and Kelly RB (1983) A molecular description of nerve terminal function. Ann Rev Biochem 52: 871–926.

    Article  PubMed  CAS  Google Scholar 

  • Rice SO (1944) Mathematical analysis of random noise. Bell Tech Syst J 23: 282–332.

    Google Scholar 

  • Schiebler W, Jahn R, Doucet JP, Rothlein J and Greengard P (1986) Characterization of synapsin I binding to small synaptic vesicles. J Biol Chem 261: 8383–8390.

    PubMed  CAS  Google Scholar 

  • Segal JR, Ceccarelli B, Fesce R and Hurlbut WP (1985) Miniature endplate potential frequency and amplitude determined by an extension of Campbell’s theorem. Biophys J 47: 183–202.

    Article  PubMed  CAS  Google Scholar 

  • Schwarz EA (1987) Depolarization without calcium can release y-aminobutyric acid from a retinal neuron. Science 238: 350–355.

    Article  Google Scholar 

  • Tauc L (1982) Non-vesicular release of neurotransmitter. Physiol Rev 62: 857–893.

    PubMed  CAS  Google Scholar 

  • Torri-Tarelli F, Grohovaz F, Fesce R and Ceccarelli B (1985) Temporal coincidence between synaptic vesicle fusion and quantal secretion of acetylcholine. J Cell Biol 101: 1386–1399.

    Article  PubMed  CAS  Google Scholar 

  • Torri-Tarelli F, Haimann C and Ceccarelli B (1987) Coated vesicles and pits during enhanced quantal release of acetylcholine at the neuromuscular junction. J Neurocytol 16: 205–214.

    Article  PubMed  CAS  Google Scholar 

  • Ueda T and Greengard P (1977) Adenosine 31:51 - monophosphate-regulated phosphoprotein system of neuronal membranes. I. Solubilization, purification, and some properties of an endogenous phosphoprotein. J Biol Chem 252:5155– 5163.

    Google Scholar 

  • Valtorta F, Jahn R, Fesce R, Greengard P and Ceccarelli B (1988) Synaptophysin (p38) at the frog neuromuscular junction: its incorporation into the axolemma and recycling after intense quantal secretion. J Cell Biol, submitted.

    Google Scholar 

  • Valtorta F, Villa A, Jahn R, De Camilli P, Greengard P and Ceccarelli B (1987) Localization of synapsin I at the frog neuromuscular junction. Neurosci, in press.

    Google Scholar 

  • Verveen AA and De Felice LJ (1974) Membrane noise. Progr Biophys Mol Biol 28: 189–268.

    Article  CAS  Google Scholar 

  • Vyskocil R and Illes P (1979) Non-quantal release of transmitter at mouse neuromuscular junction and its dependence on the activity of Na -K -ATPase. Pfluegers Arch Europ J Physiol 370: 295–297.

    Article  Google Scholar 

  • Wanke E, Ferroni A, Gattanini P and Meldolesi J (1986) Alpha-latrotoxin of Black Widow Spider Venom opens a small, non-closing cation channel. Bioch Biophys Res Comm 134: 320–325.

    Article  CAS  Google Scholar 

  • Whittaker VP, Michaelson IA and Kirkland RJ (1964) The separation of synaptic vesicles from nerve ending particles (“synaptosomes”). Biochem J 90: 293–303.

    PubMed  CAS  Google Scholar 

  • Wiedemann B and Franke W (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein of M 38,000 characteristic of presynaptic vesicles. Cell 41: 1017–1028.

    Article  Google Scholar 

  • Zimmerberg J, Curran M, Cohen FS and Brodwick M (1987) Simultaneous electrical and optical measurements show that membrane fusion precedes secretory granule swelling during exocytosis of beige mouse mast cells. Proc Natl Acad Sci USA 84: 1585–1589.

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann H (1979) Vesicle recycling and transmitter release. Neurosci 4: 1773–1804.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ceccarelli, B., Valtorta, F., Hurlbut, W.P. (1988). New Evidence Supporting the Vesicle Hypothesis for Quantal Secretion at the Neuromuscular Junction. In: Zimmermann, H. (eds) Cellular and Molecular Basis of Synaptic Transmission. NATO ASI Series, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73172-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73172-3_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73174-7

  • Online ISBN: 978-3-642-73172-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics