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The Origin and Some Possible Mechanisms of the Release of Acetylcholine at Synapses

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Metabolic Compartmentation and Neurotransmission

Abstract

Very shortly after the enunciation of the quantal theory of synaptic transmission by Del Castillo and Katz (1954), small vesicles were observed in the synaptic region by electron microscopy (De Robertis and Bennett, 1955). It seemed reasonable, as suggested by De Castillo and Katz (1955), that these vesicles were the morphological counterparts of the quanta, and it was envisaged that they could quantitatively release their contents into the synaptic cleft by reverse micropinocytosis or exocytosis (Del Castillo and Katz, 1957). The demonstration by Whittaker et al. (1964) that these vesicles did indeed contain the neurotransmitter acetylcholine strengthened the vesicular hypothesis, but despite considerable attention from investigators there remain difficulties with it. This chapter describes some of the problems with the vesicular hypothesis as applied to the cholinergic system and suggests an alternative mechanism of release that might bear consideration, even though it is not without its own difficulties.

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References

  • Armstrong, C. M., 1966, Time course of TEA+-induced anomalous rectification in squid giant axon, J. Gen. Physiol 50: 491–503.

    Article  Google Scholar 

  • Babel-Guerin, E., 1974, Metabolism du calcium et liberation de l’acetylcholine dans l’organe élétrique de la torpille, J. Neurochem 23: 525–532.

    Article  Google Scholar 

  • Barker, L. A., Dowdall, M. J., and Whittaker, V. P., 1972, Choline metabolism in the cerebral cortex of guinea pigs, Biochem. J 130: 1063–1080.

    Google Scholar 

  • Barlow, R. B., Lowe, B. M., Pearson, J. D. M., Rendall, H. M., and Thompson, G. M., 1971, Ion size and activity at acetylcholine receptors, Mol. Pharmacol 7: 357–366.

    Google Scholar 

  • Barnard, E. A., Wieckowski, J., and Chiu, T. M., 1971, Cholinergic receptor molecules and cholinesterase molecules at mouse skeletal muscle junction, Nature (London) 234: 207–209.

    Article  Google Scholar 

  • Birks, R., 1971, Effects of stimulation on synaptic vesicles in sympathetic ganglia as shown by fixation in the presence of Mg2+s, J. Physiol (London) 216: 26–28 P.

    Google Scholar 

  • Birks, R. I., 1974, The relationship of transmitter release and storage to fine structure in a sympathetic ganglion, J. Neurocytol 3: 133–160.

    Article  Google Scholar 

  • Birks, R., and Macintosh, F. C., 1961, Acetylcholine metabolism of a sympathetic ganglion, Can. J. Biochem. Physiol 39: 788–827.

    Article  Google Scholar 

  • Canepa, D. G., Pauling, P., and Sorum, H., 1966, Structure of acetylcholine and other substrates of cholinergic systems, Nature (London) 210: 907–909.

    Article  Google Scholar 

  • Ceccarelli, B., Hurlbut, W. P., and Mauro, A., 1973, Turnover of transmitter and synpatic vesicles at the frog neuromuscular junction, J. Cell Biol 57: 499–524.

    Article  Google Scholar 

  • Collier, B., and Macintosh, F. C., 1969, The source of choline for acetylcholine synthesis in a sympathetic ganglion, Can. J. Physiol Pharmacol 47: 127–135.

    Article  Google Scholar 

  • Collier, B., Poon, P., and Salehmoghaddam, S., 1972, The formation of choline and of acetylcholine by brain in vitro, J. Neurochem 19: 51–60.

    Article  Google Scholar 

  • Del Castillo, J., and Katz, B., 1954, Quantal components of the end plate potential, J. Physiol (London) 124: 560–573.

    Google Scholar 

  • Del Castillo, J., and Katz, B., 1955, Local activity at a depolarized nerve-muscle junction, J. Physiol (London) 128: 396–411.

    Google Scholar 

  • Del Castillo, J., and Katz, B., 1957, Microphysiologie comparée des éléments excitables’. La base ‘quantale’ de la transmission neuromusculaire, Coll. Int. C.N.R.S 67: 245–258.

    Google Scholar 

  • De Robertis, E. D. P., and Bennett, H. S., 1955, Some features of the submicroscopic morphology of synapses in frog and earthworm, J. Biophys. Biochem. Cytol 1: 47–58.

    Article  Google Scholar 

  • Dowdall, M. J., and Zimmermann, H., 1974, Evidence for heterogenous pools of acetylcholine in isolated cholinergic synaptic vesicles, Brain Res. 71: 160–166.

    Article  Google Scholar 

  • Dunant, Y., Gautron, J., Israël, M., Lesbats, B., and Manaranche, R., 1972, Les compartiments d’acétylcholine de l’organe élétrique de la torpille et leurs modifications par la stimulation, J. Neurochem 19: 1987–2002.

    Article  Google Scholar 

  • Dunant, Y., Gautron, J., Israël, M., Lesbats, B., and Manaranche, R., 1974, Evolution de la décharge de l’organe élétrique de la torpille et variation simultanées de l’acétylcholine au cours de la stimulation, J. Neurochem 23: 635–643.

    Article  Google Scholar 

  • Elmquist, D., and Quastel, D. M. J., 1965a, Presynaptic action of hemicholinium at the neuromuscular junction, J. Physiol (London) 177: 463–482.

    Google Scholar 

  • Elmquist, D., and Quastel, D. M. J., 1965b, A quantitative study of end plate potentials in isolated human muscle, J. Physiol (London) 178: 505–529.

    Google Scholar 

  • Fonnum, F., 1967, The ‘compartmentation’ of choline acetyltransferase within the synaptosome, Biochem. J 103: 262–270.

    Google Scholar 

  • Frost, A. A., and Pearson, R. G., 1961, “Kinetic Mechanisms,” 2nd edition, John Wiley & Sons, New York.

    Google Scholar 

  • Haga, T., 1971, Synthesis and release of (14C) acetylcholine in synaptsomes, J. Neurochem 18: 781–798.

    Article  Google Scholar 

  • Hauser, H., Phillips, M. C., and Marchbanks, R. M., 1970, Physical studies of the interactions of acetylcholine chloride with membrane constituents, Biochem. J 120: 329–335.

    Google Scholar 

  • Heuser, J. E., and Reese, T. S., 1973, Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction, J. Cell Biol 57: 315–344.

    Article  Google Scholar 

  • Hille, B., 1970, Ionic channels in nerve membranes, Prog. Biophys. Mol. Biol 21: 1–32.

    Article  Google Scholar 

  • Hodgkin, A. L., and Keynes, R. D., 1955fl, Active transport of cations in giant axons from Sepia and Loligo, J. Physiol (London) 128: 28–60.

    Google Scholar 

  • Hodgkin, A. L., and Keynes, R. D., 1955b, Potassium permeability of a giant nerve fibre, J. Physiol. (London) 128: 61–88.

    Google Scholar 

  • Hubbard, J. I., 1970, Mechanism of transmitter release, Prog. Biophys. Mol Biol 21: 33–124.

    Article  Google Scholar 

  • Israël, M., and Tu£ek, S., 1974, Utilization of acetate and pyruvate for the synthesis of ‘total’ ‘bound’ and ‘free’ acetylcholine in the electric organ of Torpedo, J. Neurochem 22: 487–493.

    Article  Google Scholar 

  • Israël, M., Hirt, L., and Mastour-Frachon, P., 1973, Métabolism et échange d’acétylcholine dans les terminaisons nerveuses de l’organe éléctrique de la Torpille, C.R. Acad. Sci 276: 2725–2728.

    Google Scholar 

  • Jones, S. F., and Kwanbunbumpen, S., 1970a, The effects of nerve stimulation and hemicholinium on synaptic vesicles at the mammlian neuromuscular junction, J. Physiol (London) 207: 31 - 50.

    Google Scholar 

  • Jones, S. F., and Kwanbunbumpen, S., 1970b, Some effects of nerve stimulation and hemicholinium on quantal transmitter release at the mammalian neuromuscular junction, J. Physiol. (London) 207: 51–61.

    Google Scholar 

  • Katz, B., 1966, “Nerve, Muscle and Synapse,” McGraw-Hill, New York.

    Google Scholar 

  • Katz, B., and Miledi, R., 1965c, Propagation of electric activity in motor nerve terminals, Proc. R. Soc. London Ser. B 161: 453–482.

    Article  Google Scholar 

  • Katz, B., and Miledi, R., 1965b, The measurement of synaptic delay and the time course of acetylcholine release at the neuromuscular junction, Proc. R. Soc. London Ser. B 161: 483–495.

    Article  Google Scholar 

  • Katz, B., and Miledi, R., 1972, The statistical nature of the acetylcholine potential and its molecular components, J. Physiol. (London) 224: 665–699.

    Google Scholar 

  • Katz, B., and Miledi, R., 1973, The binding of acetylcholine to receptors and its removal from the synaptic cleft, J. Physiol (London) 231: 549–574.

    Google Scholar 

  • Kewitz, H., Dross, K., and Pleul, O., 1974, Choline and its Metabolic Successors in brain, in “Central Nervous System” (E. Genazzani and H. Herken, eds.), pp. 21–32, Springer-Verlag, Berlin.

    Google Scholar 

  • Kopin, I. J., Breese, G. R., Krauss, K. R., and Weise, V. K., 1968, Selective release of newly synthesized norepinephrine from the cat spleen during sympathetic nerve stimulation, J. Pharmacol Exp. Ther. 161:271–278.

    Google Scholar 

  • Landmesser, L., and Pilar, G., 1972, The onset and development of transmission in the chick ciliary ganglion, J. Physiol (London) 222: 691–713.

    Google Scholar 

  • Marchbanks, R. M., 1967, The osmotically sensitive potassium and sodium compartments of synaptosomes, Biochem. J 104: 148–157.

    Google Scholar 

  • Marchbanks, R. M., 1968A, Exchangeability of radioactive acetylcholine with the bound acetylcholine of synaptosomes and synaptic vesicles, Biochem. J 106: 87–95.

    Google Scholar 

  • Marchbanks, R. M., 1968b, The uptake of [14C] choline into synaptosomes in vitro, Biochem. J 110: 533–541.

    Google Scholar 

  • Marchbanks, R. M., 1969, The conversion of 14C-choline into 14C-acetylcholine in synaptosomes in vitro, Biochem. Pharmacol 18: 1763–1766.

    Article  Google Scholar 

  • Marchbanks, R. M., and Israel, M., 1971, Aspects of acetylcholine metabolism in the electric organ of Torpedo marmorata, J. Neurochem 18: 439–448.

    Article  Google Scholar 

  • Marchbanks, R. M., and Israel, M., 1972, The heteogeneity of bound acetylcholine and synaptic vesicles, Biochem. J 129: 1049–1061.

    Google Scholar 

  • Marchbanks, R. M., and Israel, M., 1973, The association of recently synthesized acetylcholine with synaptic vesicles, Trans. Biochem. Soc 1: 131–134.

    Google Scholar 

  • Miledi, R., and Potter, L. T., 1971, Acetylcholine receptors in muscle fibres, Nature (London) 233: 599–603.

    Article  Google Scholar 

  • Miledi, R., Molinoff, P., and Potter, L. T., 1971, Isolation of the cholinergic receptor protein of Torpedo electric tissue, Nature (London) 229: 554–557.

    Article  Google Scholar 

  • Molenaar, P. C., Polak, R. L., and Nickolson, V. J., 1973, Subcellular localization of newly-formed [3H] acetylcholine in rat cerebral cortex in vitro, J. Neurochem 21: 667–678.

    Article  Google Scholar 

  • Moore, J. W., Narahashi, T., and Shaw, T. I., 1967, An upper limit to the number of sodium channels in nerve membrane, J. Physiol (London) 188: 99–105.

    Google Scholar 

  • Partington, P., Feeney, J., and Burgen, A. S. V., 1972, The conformation of acetylcholine and related compounds in aqueous solution as studied by nuclear magnetic resonance spectroscopy, Mol. Pharmacol 8: 269–277.

    Google Scholar 

  • Potter, L. T., 1970, Synthesis, storage and release of 14C acetylcholine in isolated rat diaphragm muscles, J. Physiol (London) 206: 145–166.

    Google Scholar 

  • Richter, J. A., and Marchbanks, R. M., 1971a, Synthesis of radioactive acetylcholine from [3H] choline and its release from cerebral cortex slices in vitro, J. Neurochem 18: 691–703.

    Article  Google Scholar 

  • Richter, J. A., and Marchbanks, R. M., 1971b, Isolation of 3H acetylcholine pools by subcellular fractionation of cerebral cortex slices incubated with 3H choline, J. Neurochem 18: 705–712.

    Article  Google Scholar 

  • Ritchie, A., and Goldberg, A. M., 1970, Vesicular and synaptoplasmic synthesis of acetylcholine, Science 169: 489–490.

    Article  Google Scholar 

  • Sparf, B., 1973, On the turnover of acetylcholine in the brain, Acta Physiol Scand. Suppl 397: 1–47.

    Google Scholar 

  • Tauc, L., Hoffmann, A., Tsuji, S., Hinzen, D. H., and Faille, L., 1974, Transmission abolished in a cholinergic synapse after injection of acetylcholinesterase into a presynaptic neuron, Nature (London) 250: 496–498.

    Article  Google Scholar 

  • Whittaker, V. P., Michaelson, I. A., and Kirland, R. J. A., 1964, The separation of synaptic vesicles from nerve ending particles (‘synaptosomes’), Biochem. J 90: 293–303.

    Google Scholar 

  • Zimmermann, H., and Whittaker, V. P., 1974a, Effect of electrical stimulation on the yield and composition of synaptic vesicles from the cholinergic synapses of the electric organ of Torpedo: A combined biochemical, electrophysiological and morphological study, J. Neurochem 22: 435–450.

    Article  Google Scholar 

  • Zimmermann, H., and Whittaker, V. P., 1974b, Different recovery rates of the electrophysiological, biochemical and morphological parameters in the cholinergic synapses of the Torpedo electric organ after stimulation, J. Neurochem. 22: 1109–1114.

    Article  Google Scholar 

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Marchbanks, R.M. (1975). The Origin and Some Possible Mechanisms of the Release of Acetylcholine at Synapses. In: Berl, S., Clarke, D.D., Schneider, D. (eds) Metabolic Compartmentation and Neurotransmission. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4319-6_37

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  • DOI: https://doi.org/10.1007/978-1-4613-4319-6_37

  • Publisher Name: Springer, Boston, MA

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