Abstract
During a Symposium in Philadelphia in 1954, Sir Henry Dale discussed the beginnings of chemical transmission and told us that before Otto Loewi’s discovery in 1921 the general climate of physiological opinion still remained hesitant and sceptical. “Transmission by chemical mediators” Sir Henry Dale said “was like a lady with whom the neurophysiologist was willing to live and to consort in private, but with whom he was reluctant to be seen in public”. Progress since then has been more than spectacular, and today nobody doubts that the transmission from motor nerve to skeletal muscle is chemical and that the transmitter substance is acetylcholine. After its release the acetylcholine diffuses across the synaptic gap and acts on a component of the post-synaptic membrane, the so-called acetylcholine receptor. The molecular properties of these receptors at the neuromuscular junction have been intensively studied during the last three years and the evidence that they exist as actual chemical substances is now quite strong1.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ali, H-H., Utting, J.E., Gray, C.: Stimulus frequency in the detection of neuromuscular block in humans. Brit. J. Anaesth. 42, 967–978 (1970).
Ben-Haim, D., Landau, E.M., Silman, I.: The role of a reactive disulphide bond in the function of the acetylcholine receptor at the frog neuromuscular junction. J. Physiol. (Lond.) 234, 305–325 (1973).
Bennett, G., Tyler, C., Zaimis, E.: Mecamylamine and its mode of action. Lancet 1957 I, 218–222.
Bigland, B., Goetzee, B., Maclagan, J., Zaimis, E.: The effect of lowered muscle temperature on the action of neuromuscular blocking drugs. J. Physiol. (Lond.) 141, 425–434 (1958).
Bovet, D.: Some aspects of the relationship between chemical constitution and curare-like activity. Ann. N.Y. Acad. Sci. 54, 407–437 (1951).
Brown, G. L., Dale, H.H., Feldberg, W.: Reactions of the normal mammalian muscle to acetylcholine and to eserine. J. Physiol. (Lond.) 87, 394–424 (1936).
Burns, B.D., Paton, W.D.M.: Depolarisation of the motor end-plate by decamethonium and acetylcholine. J. Physiol. (Lond.) 115, 41–73 (1951).
Cannard, T.H., Zaimis, E.: The effect of lowered muscle temperature on the action of neuromuscular blocking drugs in man. J. Physiol. (Lond.) 149, 112–119 (1959).
Churchill-Davidson, H.C.: The changing pattern of neuromuscular block. Canad. Anaesth. Soc.J. 8, 91–98 (1961).
Churchill-Davidson, H.C., Christie, T.H., Wise, R.P.: Dual neuromuscular block in man. Anesthesiology 21, 144–149 (1960).
Churchill-Davidson, H.C., Katz, R.L.: Dual, phase II, or desensitization block? Anesthesiology 27, 536–538 (1966).
Cohen, P. J., Heisterkamp, D. V., Skovsted, P.: The effect of general anaesthetics on the response to tetanic stimulus in man. Brit. J. Anaesth. 42, 543–547 (1970).
Crul, J.F., Long, G.J., Brunner, E.A., Coolen, J.M.W.: The changing pattern of neuromuscular blockade caused by succinylcholine in man. Anesthesiology 27, 729–735 (1966).
Dale, H.H.: The beginnings and the prospects of neurohumoral transmission. Pharmacol. Rev. 6, 7–13 (1954).
De Jong, R.H., Freund, F.G.: Characteristics of the neuromuscular block with succinylcholine and decamethonium in man. Anesthesiology 28, 583–591 (1967).
Douglas, W.W., Paton, W.D.M.: The mechanisms of motor end-plate depolarization due to a cholinesterase-inhibiting drug. J. Physiol. (Lond.) 124, 325–344 (1954).
Eccles, J.C., Katz, B., Kuffler, S.W.: Effect of eserine on neuromuscular transmission. J. Neurophysiol. 5, 211–230 (1942).
Elmqvist, D., Thesleff, S.: Ideas regarding receptor desensitization at the motor end-plate. Rev. canad. Biol. 21, 229–234 (1962).
Feng, T.P., Li, T.H.: Studies on the neuromuscular junction. XXIII. A new aspect of the phenomena of eserine potentiation and post-tetanic facilitation in mammalian muscles. Chin. J. Physiol. 16, 37–56 (1941).
Fogdall, R.P., Miller, R.D.: Neuromuscular effects of enflurane, alone and combined with d-tubocurarine, pancuronium, and succinylcholine, in man. Anesthesiology 42, 173–178 (1975).
Foldes, F.: The pharmacology of neuromuscular blocking agents in man. Clin. Pharmacol. Ther. 1, 345–395 (1960).
Foldes, F.F., Machaj, T.S., Hunt, R.D., McNall, P.G., Carberry, P.C., Irvington, M.J.: Synthetic muscle relaxants in anesthesia. J. Amer. med. Ass. 150, 1559–1566 (1952).
Foldes, F.F., Wnuch, A.L., Hamer Hodges, R.J., Thesleff, S., Debeer, E.J.: The mode of action of depolarizing relaxants. Anesth. Analg. Curr. Res. 36, 23 (1957).
Hall, R.A., Parkes, M.W.: The effect of drugs upon neuromuscular transmission in the guinea-pig. J. Physiol. (Lond.) 122, 274–281 (1953).
Jenden, D.J.: Effect of drugs upon neuromuscular transmission in the isolated guinea-pig diaphragm. J. Pharmacol. exp. Ther. 114, 398–408 (1955).
Karlin, A.: Chemical modification of the active site of the acetylcholine receptor. J. gen. Physiol. 54, 245–264 (1969).
Karlin, A., Bartels, E.: Effects of blocking sulphydryl groups and of reducing disulfide bonds on the acetylcholine-activated permeability system of the electroplax. Biochim. biophys. Acta (Amst.) 126, 525–535 (1966).
Karlin, A., Winnik, M.: Reduction and specific alkylation of the receptor for acetylcholine. Proc. nat. Acad. Sci. (Wash.) 60, 668–674 (1968).
Katz, B.: The release of neural transmitter substances. Liverpool: University Press 1969.
Katz, R.L.: Modification of the action of pancuronium by succinylcholine and halothane. Anesthesiology 35, 602–606 (1971).
Katz, R.L.: Electromyographic and mechanical effects of suxamethonium and tubocurarine on twitch, tetanic and post-tetanic responses. Brit. J. Anaesth. 45, 849–859 (1973).
Katz, R.L., Ryan, J.F.: The neuromuscular effects of suxamethonium in man. Brit. J. Anaesth. 41, 381–390 (1969).
Katz, R.L., Wolf, C.E., Papper, E.M.: The nondepolarizing neuromuscular blocking action of succinylcholine in man. Anesthesiology 24, 784–789 (1963).
Lebowitz, M.H., Blitt, C.D., Walts, L.F.: Depression of twitch response to stimulation of the ulnar nerve during Ethrane anesthesia in man. Anesthesiology 33, 52–57 (1970).
Loewi, O.: Über humorale Übertragbarkeit der Herznervenwirkung. Pflügers Arch. ges. Physiol. 189, 239–242 (1921).
Maclagan, J.: A comparison of the responses of the tenuissimus muscle to neuromuscular blocking drugs in vivo and in vitro. Brit. J. Pharmacol. 18, 204–216 (1962).
Magazanik, L.G., Vyskočil, F.: The loci of α-bungarotoxin action on the muscle postjunctional membrane. Brain. Res. 48, 420–423 (1972).
Magazanik, L.G., Vyskočil, F.: Desensitization at the motor end-plate. In: Rang, H.P. (Ed.), Drug Receptors, pp. 105–119. London: Macmillan 1973.
Masland, R.L., Wigton, R.S.: Nerve activity accompanying fasciculation produced by prostigmine. J. Neurophysiol. 3, 269–275 (1940).
Michelson, M.J., Zeimal, E.V.: Acetylcholine: an approach to the molecular mechanism of action. Oxford: Pergamon Press 1973.
Miledi, R.: The acetylcholine sensitivity of frog muscle fibres after complete and partial denervation. J. Physiol. (Lond.) 151, 1–23 (1960a).
Miledi, R.: Junctional and extra-junctional acetylcholine receptors in skeletal muscle fibres. J. Physiol. (Lond.) 151, 24–30 (1960b).
Miller, R.D., Eger, E. I., Way, W. L., Stevens, W.C., Dolan, W. M.: Comparative neuromuscular effects of forane and halothane alone and in combination with d-tubocurarine in man. Anesthesiology 35, 38–42 (1971).
Nastuk, W.L., Manthey, A. A., Gissen, A. J.: Activation and inactivation of postjunctional membrane receptors. Ann. N.Y. Acad. Sci. 137, 999–1014 (1966).
Otsuka, M., Endo, M., Nonomura, J.: Presynaptic nature of neuromuscular depression. Jap. J. Physiol. 12, 573–584 (1962).
Paton, W.D.M.: Mode of action of neuromuscular blocking agents. Brit. J. Anaesth. 28, 470–480 (1956).
Paton, W.D.M., Waud, D.R.: Drug-receptor interactions at the neuromuscular junction. In: Dereuck, A.V.S. (Ed.): Curare and Curare-like Agents. Ciba Foundation Study Group No. 12, pp. 34–54. London: Churchill 1962.
Paton, W.D.M., Zaimis, E.: The pharmacological actions of polymethylene bistrimethylammonium salts. Brit. J. Pharmacol. 4, 381–400 (1949).
Rang, H.P.: Acetylcholine receptors. Quart. Rev. Biophys. 7, 283–399 (1975).
Rang, H.P., Ritter, J.M.: The effect of disulphide bond reduction on the properties of cholinergic receptors in chick muscle. Molec. Pharmacol. 7, 620–631 (1971).
Richards, H., Youngman, H.R.: The ultra-short-acting relaxants. Brit. med. J. 1, 1334–1335 (1952).
Riker, W.F., Jr.: Actions of acetylcholine on mammalian motor nerve terminal. J. Pharmacol. exp. Ther. 152, 397–416 (1966).
Suarez-Kurtz, G., Paulo, L.G., Fonteles, M. C.: Further studies on the neuromuscular effects of β-diethylaminoethyl-diphenyl propylacetate hydrochloride (SKF-525-A). Arch. int. Pharmacodyn. 177, 185–195 (1969).
Thesleff, S.: Neuromuscular block caused by acetylcholine. Nature (Lond.) 175, 594–595 (1955a).
Thesleff, S.: The mode of neuromuscular block caused by acetylcholine, nicotine, decamethonium and succinylcholine. Acta physiol. scand. 34, 218–231 (1955b).
Thesleff, S.: Motor end-plate “desensitization” by repetitive nerve stimuli. J. Physiol. (Lond.) 148, 659–664 (1959).
Thesleff, S.: Nervous control of chemosensitivity in muscle. Ann. N.Y. Acad. Sci. 94, 535–546 (1961).
Vernikos-Danellis, J., Zaimis, E.: Some pharmacological actions of bretylium and guanethidine. Lancet 1960 2, 787–788.
Walts, L.F., Dillon, J.B.: Clinical studies on succinylcholine chloride. Anesthesiology 28, 372–376 (1967).
White, D.C.: Dual block after intermittent suxamethonium. Brit. J. Anaesth. 35, 305–312 (1963).
Zaimis, E.: Motor end-plate differences as a determining factor in the mode of action of neuromuscular blocking substances. J. Physiol. (Lond.) 122, 238–251 (1953).
Zaimis, E.: The interruption of neuromuscular transmission and some of its problems. Pharmacol. Rev. 6, 53–57 (1954).
Zaimis, E.: Mechanisms of neuromuscular blockade. In: Bovet, D., Bovet-Nitti, F., Marini-Bettolo, G.B. (Eds.): Curare and Curare-Like Agents, pp. 191–203. Amsterdam: Elsevier 1959.
Zaimis, E.: Parallelism of changes produced by cooling and by drugs known to affect adrenergic mechanisms. Nature (Lond.) 187, 213–216 (1960).
Zaimis, E.: Experimental hazards and artefacts in the study of neuromuscular blocking drugs. In: Dereuck, A.V.S. (Ed.): Curare and Curare-like Agents. Ciba Foundation Study Group No. 12, pp. 75–82. London: Churchill 1962.
Zaimis, E., Metaxas, N., Havard, C.W.H., Campbell, E.D.R.: Cardiovascular and skeletal muscle changes in cats treated with thyroxine. In: Research in Muscular Dystrophy, pp. 301–311. Edited by Members of the Research Committee of the Muscular Dystrophy Group. London: Pitman Medical 1965.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1976 Springer-Verlag Berlin · Heidelberg
About this chapter
Cite this chapter
Zaimis, E. (1976). The Neuromuscular Junction: Areas of Uncertainty. In: Zaimis, E., Maclagan, J. (eds) Neuromuscular Junction. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 42. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45476-9_1
Download citation
DOI: https://doi.org/10.1007/978-3-642-45476-9_1
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-45478-3
Online ISBN: 978-3-642-45476-9
eBook Packages: Springer Book Archive