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Neuromuscular Transmission—The Transmitter-Receptor Combination

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The Peripheral Nervous System

Abstract

Our understanding of neuromuscular transmission has improved greatly since the classic experiments of Claude Bernard (1856) showing that injection of curare produced paralysis in frog leg muscle and that the curare-poisoned leg muscle could not be stimulated electrically via its nerve, but was fully sensitive to direct electrical stimulation. Almost 50 years later, Langley (1906) demonstrated that nicotine stimulated skeletal muscles and its action was blocked by curare, and introduced the term “receptive substance” to define the site of action of these drugs. Evidence of cholinergic transmission at the neuromuscular junctions of skeletal muscles was obtained by Dale et al. (1936), who recovered ACh from the perfusate of neuromuscular preparations following nerve stimulation and produced twitchlike contraction in the muscle following close arterial injection of ACh. Until recently, the notion of the AChreceptor was essentially an operational term, but opinions differed as to its precise nature. The advent of improved electrophysiological techniques, such as the microelectrode (which made intracellular recording possible) and iontophoresis (with which the amount of applied agent was controlled) as well as voltage clamp techniques, helped accumulate data essential for the models of neuromuscular transmission.

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References

  • Ariens, E. J., 1954, Affinity and intrinsic activity in the theory of competitive inhibition. Part I. Problems and theory, Arch. Int. Pharmacodyn. 99:32.

    PubMed  CAS  Google Scholar 

  • Axelsson, J., and Thesleff, S., 1958, The “desensitizing” effect of acetylcholine on the mammalian motor end-plate, Acta Physiol. Scand. 43:15.

    Article  PubMed  CAS  Google Scholar 

  • Bartels, E., and Nachmansohn, D., 1965, Molecular structure determining the action of local anesthetics on the acetylcholine receptor, Biochem. Z. 342:359.

    PubMed  CAS  Google Scholar 

  • Bartels, E., and Nachmansohn, D., 1969, Organophosphate inhibitors of acetylcholinereceptor and -esterase tested on the electroplax, Arch. Biochem. Biophys. 133:1.

    Article  PubMed  CAS  Google Scholar 

  • Belleau, B., and DiTullio, V., 1971, Specific labelling of the curare binding sites of acetylcholinesterase and some properties of the modified enzyme, Can. J. Biochem. 49:1131.

    Article  PubMed  CAS  Google Scholar 

  • Belleau, B., DiTullio, V., and Tsai, Y.-H., 1970, Kinetic effects of leptocurares on the methanesulfonylation of acetylcholinesterase: A correlation with pharmacodynamic properties, Mol. Pharmacol. 6:41.

    PubMed  CAS  Google Scholar 

  • Bennett, M. V. L., Wurzel, M., and Grundfest, H., 1961, The electrophysiology of electric organs of marine electric fishes, J. Gen. Physiol. 44:757.

    Article  PubMed  CAS  Google Scholar 

  • Berg, D. K., Kelly, R. B., Sargent, P. B., Williamson, P., and Hall, Z. W., 1972, Binding of a ±-bungarotoxin to acetylcholine receptors in mammalian muscle, Proc. Natl. Acad. Sci. USA 69:147.

    Article  PubMed  CAS  Google Scholar 

  • Bernard, C., 1856, Analyse physiologique des propriétés des systèmes musculaire et nerveux au moyen du curare, Compt. Rend. Hebd. Séanc. Acad. Sci. Paris 43:825.

    Google Scholar 

  • Bertolini, A., Greggia, A., and Ferrari, W., 1967, Atropine-like properties of hemi-cholinium-3, Life Sci. 6:537.

    Article  PubMed  CAS  Google Scholar 

  • Burgen, A. S. V., 1965, The role of ionic interaction at the muscarinic receptor, Brit. J. Pharmacol. 25:4.

    PubMed  CAS  Google Scholar 

  • Changeux, J.-P., Podleski, T., and Meunier, J.-C., 1969, On some structural analogies between acetylcholinesterase and the macromolecular receptor of acetylcholine, J. Gen. Physiol. 54:225S.

    Article  CAS  Google Scholar 

  • Changeux, J.-P., Meunier, J.-C., and Huchet, M., 1971, Studies on the cholinergic receptor protein of Electrophorus electricus, Mol. Pharmacol. 7:538.

    PubMed  CAS  Google Scholar 

  • Clark, A. J., 1933, The Mode of Action of Drugs on Cells, Arnold, London.

    Google Scholar 

  • Dale, H. H., Feldberg, W., and Vogt, M., 1936, Release of acetylcholine at voluntary motor nerve endings, J. Physiol. Lond. 86:353.

    PubMed  CAS  Google Scholar 

  • Del Castillo, J., Rodriguez, A., and Romero, C. A., 1967, Pharmacological studies on an artificial transmitter-receptor system, Ann. N.Y. Acad. Sci. 144:803.

    Article  Google Scholar 

  • Dudai, Y., Silman, I., Kalderon, N., and Blumberg, S., 1972, Purification by affinity chromatography of acetylcholinesterase from electric organ tissue of the electric eel subsequent to tryptic treatment, Biochim. Biophys. Acta 268:138.

    PubMed  CAS  Google Scholar 

  • Eccles, J. C., 1966, The ionic mechanisms of excitatory and inhibitory synaptic action, Ann. N.Y. Acad. Sci. 137:473.

    Article  PubMed  CAS  Google Scholar 

  • Edelstein, S. J., 1972, An allosteric mechanism for the acetylcholine receptor, Biochem. Biophys. Res. Commun. 48:1160.

    Article  PubMed  CAS  Google Scholar 

  • Edwards, C., Bunch, W., Marfey, P., Marois, R., and Van Meter, D., 1970, Studies on the chemical properties of the acetylcholine receptor site of the frog neuromuscular junction, J. Membrane Biol. 2:119.

    Article  Google Scholar 

  • Ehrenpreis, S., Hehir, R. M., and Mittag, J. W., 1971, Assay and properties of essential (junctional) cholinesterases of the rat diaphragm, in: Cholinergic Ligand Interactions (D. Triggle, J. Moran, and E. Barnard, eds.), p. 67, Academic Press, New York.

    Google Scholar 

  • Eldefrawi, M. E., and Eldefrawi, A. T., 1972, Characterization and partial purification of the acetylcholine receptor from Torpedo electroplax, Proc. Natl. Acad. Sci. USA 69:1776.

    Article  PubMed  CAS  Google Scholar 

  • Eldefrawi, M. E., and Eldefrawi, A. T., 1973a, High recovery purification and molecular properties of the acetylcholine receptor from Torpedo electroplax, Arch. Biochem. Biophys. 159:362.

    Article  CAS  Google Scholar 

  • Eldefrawi, M. E., and Eldefrawi, A. T., 1973b, Cooperativities in the binding of acetylcholine to its receptor, Biochem. Pharmacol. 22:3145.

    Article  CAS  Google Scholar 

  • Eldefrawi, M. E., and O’Brien, R. D., 1971, Autoinhibition of acetylcholine binding to Torpedo electroplax; a possible molecular mechanism for desensitization, Proc. Natl Acad. Sci. USA 68:2006.

    Article  PubMed  CAS  Google Scholar 

  • Eldefrawi, M. E., Britten, A. G., and Eldefrawi, A. T., 1971a, Acetylcholine binding to Torpedo electroplax: Relationship to acetylcholine receptors, Science 173:338.

    Article  CAS  Google Scholar 

  • Eldefrawi, M. E., Britten, A. G., and O’Brien, R. D., 1971b, Action of organophosphates on binding of cholinergic ligands, Pesticide Biochem. Physiol. 1:101.

    Article  CAS  Google Scholar 

  • Eldefrawi, M. E., Eldefrawi, A. T., and O’Brien, R. D., 1971c, Binding sites for cholinergic ligands in a particulate fraction of Electrophorus electroplax, Proc. Natl. Acad. Sci. USA 68:1047.

    Article  CAS  Google Scholar 

  • Eldefrawi, M. E., Eldefrawi, A. T., Gilmour, L. P., and O’Brien, R. D., 1971d, Multiple affinities for binding of cholinergic ligands to a particulate fraction of Torpedo electroplax, Mol. Pharmacol. 7:420.

    CAS  Google Scholar 

  • Eldefrawi, M. E., Eldefrawi, A. T., Seifert, S., and O’Brien, R. D., 1972, Properties of Lubrol-solubilized acetylcholine receptor from Torpedo electroplax, Arch. Biochem. Biophys. 150:210.

    Article  PubMed  CAS  Google Scholar 

  • Ellman, G. L., Courtney, K. D., Andres, V., Jr., Featherstone, R. M., 1961, A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol. 7:88.

    Article  PubMed  CAS  Google Scholar 

  • Fatt, P., and Katz, B., 1952, Spontaneous subthreshold activity at motor nerve endings, J. Physiol. 117:109.

    PubMed  CAS  Google Scholar 

  • Feldberg, W., and Fessard, A., 1942, The cholinergic nature of the nerves to the electric organ of the Torpedo (Torpedo marmorata), J. Physiol. 101:200.

    PubMed  CAS  Google Scholar 

  • Ginsborg, B. L., 1967, Ion movements in junctional transmission, Pharmacol. Rev. 19:289.

    PubMed  CAS  Google Scholar 

  • Hall, Z. W., 1972, Release of neurotransmitters and their interaction with receptors, Ann. Rev. Biochem. 41:925.

    Article  PubMed  CAS  Google Scholar 

  • Hubbard, J. I., Wilson, D. F., and Miyamoto, M., 1969, Reduction of transmitter release by D-tubocurarine, Nature Lond. 223:531.

    Article  PubMed  CAS  Google Scholar 

  • Illiano, G., Tell, G. P. E., Siegel, M. I., and Cuatrecasas, P., 1973, Guanosine 3′:5′-cyclic monophosphate and the action of insulin, Proc. Nat. Acad. Sci. USA 70:2443.

    Article  PubMed  CAS  Google Scholar 

  • Jenkinson, D. H., 1960, The antagonism between tubocurarine and substances which depolarize the motor end-plate, J. Physiol. 152:309.

    PubMed  CAS  Google Scholar 

  • Jenkinson, D. H., and Nicholls, J. G., 1961, Contractures and permeability changes produced by acetylcholine in depolarized denervated muscle, J. Physiol. 159:111.

    PubMed  CAS  Google Scholar 

  • Johnson, E. W., and Parsons, R. L., 1972, Characteristics of postjunctional carbamylcholine receptor activation and inhibition, Am. J. Physiol. 222:793.

    PubMed  CAS  Google Scholar 

  • Karlin, A., and Bartels, E., 1966, Effects of blocking sulfhydryl groups and of reducing disulfide bonds on the acetylcholine-activated permeability system of the electroplax, Biochim. Biophys. Acta 126:525.

    Article  PubMed  CAS  Google Scholar 

  • Karlin, A., Prives, J., Deal, W., and Winnik, M., 1971, Affinity labeling of the acetylcholine receptor in the electroplax, J. Mol. Biol. 61:175.

    Article  PubMed  CAS  Google Scholar 

  • Karlsson, E., Heilbronn, E., and Widlung, L., 1972, Isolation of the nicotinic acetylcholine receptor by biospecific chromatography on insolubilized Naja naja neurotoxin, FEBS Letters 28:107.

    Article  PubMed  CAS  Google Scholar 

  • Kasai, M., and Changeux, J.-P., 1971a, In vitro excitation of purified membrane fragments by cholinergic agonists. I. Pharmacological properties of the excitable membrane fragments, J. Membrane Biol. 6:1.

    Article  CAS  Google Scholar 

  • Kasai, M., and Changeux, J.-P., 1971b, In vitro excitation of purified membrane fragments by cholinergic agonists. II. The permeability change caused by cholinergic agonists, J. Membrane Biol. 6:24.

    Article  CAS  Google Scholar 

  • Kasai, M., and Changeux, J.-P., 1971c, In vitro excitation of purified membrane fragments by cholinergic agonists III. J. Membrane Biol. 6:58.

    Article  CAS  Google Scholar 

  • Kato, G., Yong, J., and Ihnat, M., 1970, NMR studies of the interaction of eserine and atropine with acetylcholinesterase, Biochem. Biophys. Res. Commun. 40:15.

    Article  PubMed  CAS  Google Scholar 

  • Kato, G., Tan, E., and Yung, J., 1972, Allosteric properties of acetylcholinesterase, Nature New Biol. 236:185.

    Article  PubMed  CAS  Google Scholar 

  • Katz, B., 1971, Quantal mechanism of neural transmitter release, Science 173:123.

    Article  PubMed  CAS  Google Scholar 

  • Katz, B., and Miledi, R., 1970, Membrane noise produced by acetylcholine, Nature 226:962.

    Article  PubMed  CAS  Google Scholar 

  • Katz, B., and Miledi, R., 1971, Further observations on acetylcholine noise, Nature New Biol. 232:124.

    Article  PubMed  CAS  Google Scholar 

  • Katz, B., and Miledi, R., 1972, The statistical nature of the acetylcholine potential and its molecular component, J. Physiol. 224:665.

    PubMed  CAS  Google Scholar 

  • Katz, B., and Thesleff, S., 1957, A study of the “desensitization” produced by acetylcholine at the motor end-plate, J. Physiol. 138:63.

    PubMed  CAS  Google Scholar 

  • Keynes, R. D., and Martins-Ferreira, H., 1953, Membrane potentials in the electroplates of the electric eel, J. Physiol. 119:315.

    PubMed  CAS  Google Scholar 

  • Kimelberg, H. K., and Papahadjopoulos, D., 1971, Interactions of basic proteins with phospholipid membranes, J. Biol. Chem. 246:1142.

    PubMed  CAS  Google Scholar 

  • Klett, R. P., Fulpius, B. W., Cooper, D., Smith, M., Reich, E., and Possani, L. D., 1973, The acetylcholine receptor. I. Purification and characterization of a macromolecule isolated from Electrophorus electricus, J. Biol. Chem. 248:6841.

    PubMed  CAS  Google Scholar 

  • Krnjevic, K., and Mitchell, J. F., 1961, The release of acetylcholine in the isolated rat diaphragm, J. Physiol. 155:246.

    PubMed  CAS  Google Scholar 

  • Langley, J. N., 1906, On the reaction of cells and of nerve endings to certain poisons, chiefly as regards the reaction of striated muscles to nicotine and curare, J. Physiol. 20:223.

    Google Scholar 

  • Lee, C. Y., 1972, Chemistry and pharmacology of polypeptide toxins in snake venoms, Ann. Rev. Pharmacol. 12:265.

    Article  PubMed  CAS  Google Scholar 

  • Leuzinger, W., and Baker, A. L., 1967, Acetylcholinesterase. I. Large-scale purification, homogeneity, and amino acid analysis, Proc. Natl. Acad. Sci. USA 57:446.

    Article  PubMed  CAS  Google Scholar 

  • Meunier, J.-C., Olsen, R. W., Menez, A., Fromageot, P., Boquet, P., and Changeux, J.-P., 1972, Some physical properties of the cholinergic receptor protein from Electrophorus electricus revealed by a tritiated ±-toxin from Naja nigrocollis venom, Biochemistry 11:1200.

    Article  PubMed  CAS  Google Scholar 

  • Miledi, R., and Potter, L. T., 1971, Acetylcholine receptors in muscle fibers, Nature 233:599.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Nachmansohn, D., 1955, Metabolism and function of the nerve cell, Harvey Lect. (1953/1954) 49:57.

    Google Scholar 

  • Nachmansohn, D., and Lederer, E., 1939, Sur la biochemie de la Cholinesterase, Bull. Soc. Chim. Biol. (Paris) 21:797.

    CAS  Google Scholar 

  • Nemethy, G., and Scheraga, H. A., 1962, Structure of water and hydrophobic bonding in proteins. I. A model of thermodynamic properties of liquid water, J. Chem. Phys. 36:3382.

    Article  CAS  Google Scholar 

  • O’Brien, R. D., 1960, Toxic Phosphorus Esters, 434 pp., Academic Press, New York.

    Google Scholar 

  • O’Brien, R. D., Eldefrawi, M. E., and Eldefrawi, A. T., 1972, Isolation of acetylcholine receptors, Ann. Rev. Pharmacol. 12:19.

    Article  PubMed  Google Scholar 

  • Olsen, R. W., Meunier, J.-C., and Changeux, J.-P., 1972, Progress in the purification of the cholinergic receptor protein from Electrophorus electricus by affinity chromatography, FEBS Letters 28:96.

    Article  PubMed  CAS  Google Scholar 

  • Otsuka, M., Endo, M., and Nonomura, Y., 1962, Presynaptic nature of neuromuscular depression, Jap. J. Physiol. 12:573.

    Article  CAS  Google Scholar 

  • Paton, W. D. M., 1961, A theory of drug action based on the rate of drug-receptor combination, Proc. Roy. Soc. Lond. B 154:21.

    Article  Google Scholar 

  • Paton, W. D. M., and Rang, H. P., 1966, The uptake of atropine and related drugs by intestinal smooth muscle of the guinea-pig in relation to acetylcholine receptor, Proc. Roy. Soc. Lond. B 163:2.

    Google Scholar 

  • Pauling, P., and Petcher, T. J., 1972, Muscarone: An enigma resolved? Nature New Biol. 236:112.

    Article  PubMed  CAS  Google Scholar 

  • Porter, C W., Chiu, T. H., Wieckowski, J., and Barnard, E. A., 1973, Types and locations of cholinergic receptor-like molecules in muscle fiber, Nature New Biol. 241:3.

    PubMed  CAS  Google Scholar 

  • Potter, L. T., 1970, Synthesis, storage and release of C14 acetylcholine in isolated rat diaphragm muscles, J. Physiol. 206:145.

    PubMed  CAS  Google Scholar 

  • Raftery, M. A., Schmidt, J., Clark, D. G., and Wolcott, R. G., 1971, Demonstration of a specific ±-bungarotoxin binding component in Electrophorus electricus electroplax membranes, Biochem. Biophys. Res. Commun. 45:1622.

    Article  PubMed  CAS  Google Scholar 

  • Rang, H. P., and Ritter, J. M., 1969, Disulphide bond reduction in nicotinic receptors, Brit. J. Pharmacol 37:538P.

    CAS  Google Scholar 

  • Rang, H. P., and Ritter, J. M., 1970, On the mechanism of desensitization of cholinergic receptors, Mol Pharmacol 6:357.

    PubMed  CAS  Google Scholar 

  • Rosenberry, T. L., Chang, H. W., and Chen, Y. T., 1972, Purification of acetylcholinesterase by affinity chromatography and determination of active site stoichiometry, J. Biol Chem. 247:1555.

    PubMed  CAS  Google Scholar 

  • Roufogalis, B. D., and Quist, E. E., 1972, Relative binding sites of pharmacologically active ligands on bovine erythrocyte acetylcholinesterase, Mol Pharmacol 8:41.

    PubMed  CAS  Google Scholar 

  • Salpeter, M. M., and Eldefrawi, M. E., 1973, Sizes of end-plate compartments, densities of ACh-receptor and other quantitative aspects of neuromuscular transmission, J. Histochem. Cytochem. 21:769.

    Article  PubMed  CAS  Google Scholar 

  • Salpeter, M. M., Plattner, H., and Rogers, A. W., 1972, Quantitative assay of esterases in end plate of mouse diaphragm by E. M. autoradiography, J. Histochem. Cytochem. 20:1059.

    Article  PubMed  CAS  Google Scholar 

  • Sastry, B. V. R., and Cheng, C., 1972, Dissociation constants of D- and L-lactoylcholines and related compounds at cholinergic receptors, J. Pharmacol Exptl Therap. 180:326.

    CAS  Google Scholar 

  • Schmidt, J., and Raftery, M. A., 1973, Purification of acetylcholine receptors from Torpedo californica electroplax by affinity chromatography, Biochemistry 12:852.

    Article  PubMed  CAS  Google Scholar 

  • Stephenson, R. P., 1956, A modification of receptor theory, Brit. J. Pharmacol Chemotherap. 11:379.

    CAS  Google Scholar 

  • Takeuchi, A., and Takeuchi, N., 1959, Active phase of frog’s end-plate potential, J. Neurophysiol 22:395.

    PubMed  CAS  Google Scholar 

  • Takeuchi, A., and Takeuchi, N., 1960, On the permeability of end-plate membrane during the action of transmitter, J. Physiol 154:52.

    PubMed  CAS  Google Scholar 

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  1. Section of Neurobiology and Behavior, Cornell University, Ithaca, New York, USA

    Mohyee E. Eldefrawi

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  1. Mohyee E. Eldefrawi
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  1. Department of Physiology, University of Otago, Dunedin, New Zealand

    John I. Hubbard

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© 1974 Plenum Press, New York

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Eldefrawi, M.E. (1974). Neuromuscular Transmission—The Transmitter-Receptor Combination. In: Hubbard, J.I. (eds) The Peripheral Nervous System. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8699-9_8

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  • DOI: https://doi.org/10.1007/978-1-4615-8699-9_8

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