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Low- and High-Affinity Reactions in Rapid Neurotransmission

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Abstract

Until 1950–1960, most physiologists were reluctant to accept chemical neurotransmission. They believed that chemical reactions were much too slow to account for the speed of synaptic processes. The first breakthrough was to discover the impressive velocity of acetylcholinesterase. Then, nicotinic receptors provided an example of complex ultrarapid reactions: fast activation at a low ligand affinity, then desensitization if the ligand is not rapidly removed. Here, we describe synaptic transmission as a chain of low-affinity rapid reactions, assisted by many slower regulatory processes. For starting quantal acetylcholine release, mediatophores are activated by high Ca2+ concentrations, but they desensitize at a higher affinity if Ca2+ remains present. Several mechanisms concur to the rapid removal of Ca2+ from the submembrane microdomains. Among them, the Ca2+/H+ antiport is a typical low-affinity, high-speed process that certainly contributes to the rapidity of neurotransmission.

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REFERENCES

  1. Katz, B. 1988. Looking back at the neuromuscular junction. Pages 3–9, in Seilin, L. C., et al. (eds.), Neuromuscular junction, Elsevier Science, Amsterdam.

    Google Scholar 

  2. Harvey, A. M. and MacIntosh, F. C. 1940. Calcium and synaptic transmission in a sympathetic ganglion. J. Physiol. Lond. 97:408–416.

    Google Scholar 

  3. Katz, B. 1969. The Release of Neural Transmitter Substances. University Press, Liverpool.

    Google Scholar 

  4. Zhang, C. and Zhou, Z. 2002. Ca(2+)-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons. Nat. Neurosci. 5:425–430.

    PubMed  Google Scholar 

  5. Parnas, H., Segel, L., Dudel, J., and Parnas, I. 2000. Autoreceptors, membrane potential and the regulation of transmitter release. Trends Neurosci. 23:60–68.

    PubMed  Google Scholar 

  6. Dodge, F. A. and Rahamimoff, R. 1967. Co-operative action of calcium ions in transmitter release at the neuromuscular junction. J. Physiol. Lond. 193:419–432.

    PubMed  Google Scholar 

  7. Dunant, Y., Eder, L., and Servetiadis-Hirt, L. 1980. Acetylcholine release evoked by single or a few nerve impulses in the electric organ of Torpedo. J. Physiol. Lond. 298:185–203.

    PubMed  Google Scholar 

  8. Muller, D., Loctin, F., and Dunant, Y. 1987. Inhibition of evoked acetylcholine release: Two different mechanisms in the Torpedo electric organ. Eur. J. Pharmacol. 133:225–234.

    PubMed  Google Scholar 

  9. Shoji-Kasai, Y., Yoshida, A., Sato, K., Hoshino, T., Ogura, A., Kondo, S., Fujimoto, Y., Kuwahara, R., Kato, R., and Takahashi, M. 1992. Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells. Science 256:1821–1823.

    PubMed  Google Scholar 

  10. Peters, C., Bayer, M. J., Bühler, S., Andersen, J. S., Mann, M., and Mayer, A. 2001. Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion. Nature 409:581–588.

    PubMed  Google Scholar 

  11. Bruns, D. and Jahn, R. 2002. Molecular determinants of exocytosis. Pflugers Arch. 443:333–338.

    PubMed  Google Scholar 

  12. Morel, N., Dunant, Y., and Israel, M. 2001. Neurotransmitter release through the V0 sector of V-ATPase. J. Neurochem. 79:485–488.

    PubMed  Google Scholar 

  13. Falk-Vairant, J., Corrèges, P., Eder-Colli, L., Salem, N., Roulet, E., Bloc, A., Meunier, F., Lesbats, B., Loctin, F., Synguelakis, M., Israël, M., and Dunant, Y. 1996. Quantal acetylcholine release induced by mediatophore transfection. Proc. Natl. Acad. Sci. USA 93:5203–5207.

    PubMed  Google Scholar 

  14. Dunant, Y. and Israël, M. 1998. In vitro reconstitution of neurotransmitter release. Neurochem. Res. 23:709–718.

    PubMed  Google Scholar 

  15. Bloc, A., Roulet, E., Loctin, F., and Dunant, Y. 1997. Acetylcholine release from mouse neuroblastoma cells co-transfected with mediatophore and choline acetyltransferase cDNAs. NATO ASI Series 100:175–182.

    Google Scholar 

  16. Finbow, M. E. and Pitts, J. D. 1998. Structure of the ductin channel. Biosci. Rep. 18:287–297.

    PubMed  Google Scholar 

  17. Birman, S., Israël, M., Lesbats, B., and Morel, N. 1986. Solubilization and partial purification of a presynaptic membrane protein ensuring calcium-dependent acetylcholine release from proteoliposomes. J. Neurochem. 47:433–444.

    PubMed  Google Scholar 

  18. Cavalli, A., Eder-Colli, L., Dunant, Y., Loctin, F., and Morel, N. 1991. Release of acetylcholine from Xenopus oocytes injected with nRNAs from cholinergic neurons. EMBO J. 10:1671–1675.

    PubMed  Google Scholar 

  19. Galli, T., McPherson, P. S., and De Camilli, P. 1996. The Vo sector of the V-ATPase, synaptobrevin, and synaptophysin are associated on synaptic vesicles in a Triton X-100-resistant, freeze-thawing sensitive, complex. J. Biol. Chem. 271:2193–2198.

    PubMed  Google Scholar 

  20. Shiff, G., Synguelakis, M., and Morel, N. 1996. Association of syntaxin with SNAP 25 and VAMP (synaptobrevin) in Torpedo synaptosomes. Neurochem. Int. 29:659–667.

    PubMed  Google Scholar 

  21. Katz, B. and Miledi, R. B. 1969. Tetrodotoxin-resistant electric activity in presynaptic terminals. J. Physiol. Lond. 203:459–487.

    PubMed  Google Scholar 

  22. Adams, D. J., Takeda, K., and Umbach, J. A. 1985. Inhibitors of calcium buffering depress evoked transmitter release at the squid giant synapse. J. Physiol. Lond. 369:145–159.

    PubMed  Google Scholar 

  23. Hsu, S. F., Augustine, G. J., and Jackson, M. B. 1996. Adaptation of Ca(2+)-triggered exocytosis in presynaptic terminals. Neuron 17:501–512.

    PubMed  Google Scholar 

  24. Israël, M., Meunier, F. M., Morel, N., and Lesbats, B. 1987. Calcium-induced desensitization of acetylcholine release from synaptosomes or proteoliposomes equiped with mediatophore, a presynaptic membrane protein. J. Neurochem. 49:975–982.

    PubMed  Google Scholar 

  25. Morot-Gaudry-Talarmain, Y., Diebler, M.-F., Robba, M., Lancelot, J.-C., Lesbats, B., and Israël, M. 1989. Effect of cetiedil analogs on acetylcholine and choline fluxes in synaptosomes and vesicles. Eur. J. Pharmacol. 166:427–433.

    PubMed  Google Scholar 

  26. Dunant, Y., Loctin, F., Vallée, J.-P., Parducz, A., Lesbats, B., and Israël, M. 1996. Activation and desensitization of acetylcholine release by zinc in Torpedo nerve terminals. Pflügers Arch. 432:853–858.

    Google Scholar 

  27. Dunant, Y. and Israël, M. 2000. Neurotransmitter release in rapid synapses. Biochimie 82:289–302.

    PubMed  Google Scholar 

  28. Mayer, A. 2001. What drives membrane fusion in eukaryotes? Trends. Biochem. Sci. 26:717–723.

    PubMed  Google Scholar 

  29. Llinas, R., Steinberg, I. Z., and Walton, K. 1981. Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys. J. 33:323–352.

    PubMed  Google Scholar 

  30. Blaustein, M. P. 1971. Preganglionic stimulation increases calcium uptake by sympathetic ganglia. Science 172:391–393.

    PubMed  Google Scholar 

  31. Babel-Guérin, E. 1974. Métabolisme du calcium et libération de l'acétylcholine dans l'organe électrique de la Torpille. J. Neuro-chem. 23:525–532.

    Google Scholar 

  32. Llinas, R., Sugimori, M., and Silver, R. B. 1992. Microdomains of high calcium concentration in a presynaptic terminal. Science USA 256:677–679.

    Google Scholar 

  33. Castonguay, A. and Robitaille, R. 2001. Differential regulation of transmitter release by presynaptic and glial Ca2+ internal stores at the neuromuscular synapse. J. Neurosci. 21: 1911–1922.

    PubMed  Google Scholar 

  34. McGraw, C. F., Somlyo, A. V., and Blaustein, M. P. 1980. Localization of calcium in presynaptic nerve terminals: An ultra-structure and electron microprobe analysis. J. Cell Biol. 85:228–241.

    PubMed  Google Scholar 

  35. Kostyuk, P. and Verkhratsky, A. 1994. Calcium stores in neurons and glia. Neuroscience 63:381–404.

    PubMed  Google Scholar 

  36. Neher, E. 1998. Vesicle pools and Ca2+ microdomains: New tools for understanding their roles in neurotransmitter release. Neuron 20:389–399.

    PubMed  Google Scholar 

  37. Marsal, J., Esquerda, J. E., Fiol, C., Solsona, C., and Tomas, J. 1980. Calcium fluxes in isolated pure cholinergic nerve endings from the electric organ of Torpedo marmorata. J. Physiol. Paris 76:443–457.

    PubMed  Google Scholar 

  38. Fossier, P., Baux, G., Trudeau, L. E., and Tauc, L. 1992. Involvement of Ca2+ uptake by a reticulum-like store in the control of transmitter release. Neuroscience 50:427–434.

    PubMed  Google Scholar 

  39. Couteaux, R. and Pécot-Dechavassine, M. 1973. Données ultra-structurales et cytochimiques sur le mécanisme de libération de l'acétylcholine dans la transmission synaptique. Arch. Ital. Biol. 3:231–262.

    Google Scholar 

  40. Israël, M., Manaranche, R., Marsal, J., Meunier, F. M., Morel, N., Frachon, P., and Lesbats, B. 1980. ATP-dependent calcium uptake by cholinergic synaptic vesicles isolated from Torpedo electric organ. J. Membr. Biol. 54:115–126.

    PubMed  Google Scholar 

  41. Michaelson, D. M., Ophir, I., and Angel, I. 1980. ATP-stimulated Ca2+ transport into cholinergic Torpedo synaptic vesicles. J. Neurochem. 35:116–124.

    PubMed  Google Scholar 

  42. Gonçalves, P. P., Meireles, S. M., Gravato, C., and Vale, M. G. 1998. Ca2+-H+-Antiport activity in synaptic vesicles isolated from sheep brain cortex. Neurosci. Lett. 247:87–90.

    PubMed  Google Scholar 

  43. Parducz, A. and Dunant, Y. 1993. Transient increase in calcium in synaptic vesicles after stimulation. Neuroscience 52: 27–33.

    PubMed  Google Scholar 

  44. Parducz, A., Loctín, F., Babel-Guérin, E., and Dunant, Y. 1994. Exo-endocycytotic images following tetanic stimulation at a cholinergic synapse: A role in calcium extrusion? Neuroscience 62:93–103.

    PubMed  Google Scholar 

  45. Parducz, A., Toldi, J., Joo, F., Siklos, L., and Wolff, J. R. 1987. Transient increase of calcium in pre-and postsynaptic organelles of rat superior cervical ganglion after tetanizing stimulation. Neuroscience 23:1057–1061.

    PubMed  Google Scholar 

  46. Buchs, P. A., Stoppini, L., Parducz, A., Siklos, L., and Muller, D. 1994. A new cytochemical method for the ultrastructural localization of calcium in the central nervous system. J. Neurosci. Meth. 54:83–93.

    Google Scholar 

  47. Dunant, Y., Babel-Guérin, E., and Droz, B. 1980. Calcium metabolism and acetylcholine release at the nerve-electroplaque junction. J. Physiol. Paris 76:471–478.

    PubMed  Google Scholar 

  48. Muller, D., Garcia-Segura, L. M., Parducz, A., and Dunant, Y. 1987. Brief occurrence of a population of large intramembrane particles in the presynaptic membrane during transmission of a nerve impulse. Proc. Natl. Acad. Sci. USA 84:590–594.

    PubMed  Google Scholar 

  49. Dunant, Y. 2000. Quantal acetylcholine release: Vesicle fusion or intramembrane particles? Microscopy Res. Tech. 49:38–46.

    Google Scholar 

  50. Uvnas, B. 1973. An attempt to explain nervous transmitter release as due to nerve impulse-induced ion exchange. Acta Physiol. Scand. 87:168–175.

    PubMed  Google Scholar 

  51. Rahamimoff, R. and Fernandez, J. M. 1997. Pre-and postfusion regulation of transmitter release. Neuron 18:17–27.

    PubMed  Google Scholar 

  52. Malo, M., Diebler, M. F., Prado de Carvalho, L., Meunier, F. M., Dunant, Y., Bloc, A., Stinnakre, J., Tomasi, M., Tchelingerian, J., Couraud, P. O., and Israël, M. 1999. Evoked acetylcholine release by immortalized brain endothelial cells genetically modified to express choline acetyltransferase and/or the vesicular acetylcholine transporter. J. Neurochem. 73:1483–1491.

    PubMed  Google Scholar 

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  1. Départment de Pharmacologie, Université de Genève, Centre Médical Universitaire, CH-1211, Genève-4, Switzerland

    Yves Dunant & Alain Bloc

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  1. Yves Dunant
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  2. Alain Bloc
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Correspondence to Yves Dunant.

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Dunant, Y., Bloc, A. Low- and High-Affinity Reactions in Rapid Neurotransmission. Neurochem Res 28, 659–665 (2003). https://doi.org/10.1023/A:1022806330830

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