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The Molecular Basis of Neurotransmission: Structure and Function of the Nicotinic Acetylcholine Receptor

  • Robert Anholt
  • Jon Lindstrom
  • Mauricio Montal

Abstract

Acetylcholine was identified as the first neurotransmitter as a result of elegant experiments by Otto Loewi in 1921 who demonstrated that the vagus nerve liberates a substance that has an inhibitory effect on the rate of the heartbeat of an isolated frog heart. Loewi showed that this “vagus substance” could be transferred from the fluid filling the heart onto another heart and there reproduce the same inhibitory effect. He coined the term “humoral transmission” to describe this activity (Loewi, 1921). Subsequent experiments identified the “vagus substance” as acetylcholine. It became clear that acetylcholine, in addition to its influence on the heart, exerted a variety of pharmacologically distinct effects, which were classified by Sir Henry Dale (1934) as “muscarinic” and “nicotinic” actions, because some were mimicked best by muscarine and others by nicotine. Acetylcholine receptors with muscarinic ligand-binding properties are characterized by prolonged responses of slow onset which are mediated through nucleotide cyclases (for short reviews see Sokolovsky and Bartfai, 1981; Hartzell, 1982), whereas acetylcholine receptors with nicotinic-binding properties are characterized by rapid responses in which ligand binding regulates the opening and closing of a cation-specific channel through a conformational alteration in the molecule. Acetylcholine receptors at the neuromuscular junctions of striated muscle and at the synapses of fish electric organs (which are phylogenetically related to muscle tissue) are the best-studied nicotinic acetylcholine receptors and the subjects of this review.

Keywords

Acetylcholine Receptor Nicotinic Acetylcholine Receptor Electric Organ Planar Lipid Bilayer Frog Neuromuscular Junction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams, D. J., Dwyer, T. M., and Hille, B., 1980, The permeability of endplate channels to monovalent and divalent metal cations, J. Gen. Physiol 75: 493–510.PubMedGoogle Scholar
  2. Adams, P. R., 1975, An analysis of the dose-response curve at voltage–clamped frog endplates, Pfluegers Arch. 360: 145–153.Google Scholar
  3. Albuquerque, E. X., Tsai, M.–C., Aronstam, R. S., Witkop, B., Eldefrawi, A. T., and Eldefrawi, M. E., 1980a, Phencyclidine interactions with the ionic channel of the acetylcholine receptor and electrogenic membrane, Proc. Natl. Acad. Sci. USA 77: 1224–1228.PubMedGoogle Scholar
  4. Albuquerque, E. X., Tsai, M.–C., Aronstam, R. S., Eldefrawi, A. T., and Eldefrawi, M. E., 1980b, Sites of action of phencyclidine. II. Interaction with the ionic channel of the nicotinic receptor, Mol. Pharmacol 18: 167–178.PubMedGoogle Scholar
  5. Anderson, M. J., and Cohen, M. W., 1977, Nerve–induced and spontaneous redistribution of acetylcholine receptors on cultured muscle cells, J. Physiol 268: 757–773.PubMedGoogle Scholar
  6. Anderson, C. R., and Stevens, C. F., 1973, Voltage–clamp analysis of acetylcholine produced end–plate current fluctuations at frog neuromuscular junction, J. Physiol 235: 655–691.PubMedGoogle Scholar
  7. Anderson, D. J., and Blobel, G., 1981, In vitro synthesis, glycosylation and membrane insertion of the four subunits of Torpedo acetylcholine receptor, Proc. Natl. Acad. Sci. USA 78: 5598–5602.Google Scholar
  8. Anderson, D. J., Walter, P., and Blobel, G., 1982, Signal recognition protein is required for the integration of acetylcholine receptor 8–subunit, a transmembrane glycoprotein, into the endoplasmic reticulum membrane, J. Cell Biol 93: 501–506.PubMedGoogle Scholar
  9. Anderson, D. J., Blobel, G., Tzartos, S., Gullick, W., and Lindstrom, J., 1983, Transmembrane orientation of an early biosynthetic form of acetylcholine receptor S subunit determined by proteolytic dissection in conjunction with monoclonal antibodies, J. Neurosci 3: 1773–1784.PubMedGoogle Scholar
  10. Andreasen, T. J., and McNamee, M. G., 1980, Inhibition of ion permeability control properties of acetylcholine receptor from Torpedo californica by long–chain fatty acids, Biochemistry 19: 4719–4726.PubMedGoogle Scholar
  11. Andreasen, T. J., Doerge, D. R., and McNamee, M. G., 1979, Effects of phospholipase A2 on the binding and ion permeability control properties of the acetylcholine receptor, Arch. Biochem. Biophys 194: 468–480.PubMedGoogle Scholar
  12. Anholt, R., Lindstrom, J., and Montai, M., 1980, Functional equivalence of monomeric and dimeric forms of purified acetylcholine receptor from Torpedo californica in reconstituted lipid vesicles, Eur. J. Biochem 109: 481–487.PubMedGoogle Scholar
  13. Anholt, R., Lindstrom, J., and Montai, M., 1981, Stabilization of acetylcholine receptor channels by lipids in cholate solution and during reconstitution in vesicles, J. Biol. Chem 256: 4377–4387.PubMedGoogle Scholar
  14. Anholt, R., 1981, Reconstitution of acetylcholine receptors in model membranes, Trends Biochem. Sci 6: 288–291.Google Scholar
  15. Anholt, R., Fredkin, D. R., Deerinck, T., Ellisman, M., Montai, M., and Lindstrom, J., 1982, Incorporation of acetylcholine receptors into liposomes: Vesicle structure and acetylcholine receptor function, J. Biol. Chem 257: 7122–7134.PubMedGoogle Scholar
  16. Anholt, R., Montai, M., and Lindstrom, J., 1983, Incorporation of acetylcholine receptors in model membranes: An approach aimed at studies of the molecular basis of neurotransmission, in: Peptide and Protein Reviews, Vol. 1 ( M. Hearn, ed.), Marcel Dekker, New York, pp. 95–137.Google Scholar
  17. Axelrod, D., Ravdin, P., Koppel, D. E., Schlessinger, I., Webb, W. W., Elson, E. L., and Podleski, T. R., 1976, Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers, Proc. Natl. Acad. Sci. USA 73: 4594–4598.PubMedGoogle Scholar
  18. Axelrod, D. P., Ravdin, P. M., and Podleski, T. R., 1978, Control of acetylcholine receptor mobility and distribution in cultured muscle membrane. A fluorescence study, Biochim. Biophys. Acta 511: 23–28.PubMedGoogle Scholar
  19. Ballivet, M., Patrick, J., Lee, J., and Heinemann, S., 1982, Molecular cloning of cDNA coding for the y–subunit of Torpedo acetylcholine receptor, Proc. Natl. Acad. Sci. USA 79: 4466–4470.PubMedGoogle Scholar
  20. Barnard, E. A., Miledi, R., and Sumikawa, K., 1982, Translation of exogenous messenger RNA coding for nicotinic acetylcholine receptors produces functional receptors in Xenopus oocytes, Proc. R. Soc. Lond B215: 241–246.PubMedGoogle Scholar
  21. Barrantes, F. J., 1978, Agonist–mediated changes of the acetylcholine receptor in its membrane environment, J. Mol. Biol 124: 1–26.PubMedGoogle Scholar
  22. Barrantes, F. J., 1982, Interactions of the membrane–bound acetylcholine receptor with the nonreceptor peripheral peptide, in: Neuroreceptors, Walter de Gruyter and Co., Berlin and New York, pp. 315–328.Google Scholar
  23. Barrantes, F. J., Neugebauer, D.–Ch., and Zingsheim, H. P., 1980, Peptide extraction by alkaline treatment is accompanied by rearrangement of the membrane bound acetylcholine receptor from Torpedo marmorata, FEBS Lett. 112: 73–78.PubMedGoogle Scholar
  24. Barrantes, F. J., Mieskes, J., and Wallimann, T., 1983, Creatine kinase activity in the Torpedo electrocyte and in the nonreceptor, peripheral y proteins from acetylcholine receptor–rich membranes, Proc. Natl. Acad. Sci. USA 80: 5440–5444.PubMedGoogle Scholar
  25. Bartholdi, M., Barrantes, F. J., and Jovin, T. M., 1981, Rotational molecular dynamics of the membranebound acetylcholine receptor revealed by phosphorescence spectroscopy, Eur. J. Biochem 120: 389–397.PubMedGoogle Scholar
  26. Ben-Haim, D., Landau, E. M., and Silman, I., 1973, The role of a reactive disulphide bond in the function of the acetylcholine receptor at the frog neuromuscular junction, J. Physiol 234: 305–325.Google Scholar
  27. Bennett, M. V. L., Wurzel, M., and Grundfest, H., 1961, The electrophysiology of electric organs of marine electric fishes. I. Properties of electroplaques of Torpedo nobiliana, J. Gen. Physiol 44: 757–804.PubMedGoogle Scholar
  28. Beranek, R., and Vyskocil, F., 1967, The action of tubocurarine and atropine on the normal and denervated rat diaphragm, J. Physiol 188: 53–66.Google Scholar
  29. Berg, D. K., and Hall, Z. W., 1974, Fate of a–bungarotoxin bound to acetylcholine receptors of normal and denervated muscle, Science 184: 473–475.PubMedGoogle Scholar
  30. Berg, D. K., and Hall, Z. W., 1975a, Loss of a–bungarotoxin from junctional and extrajunctional acetylcholine receptors in rat diaphragm muscle in vivo and in organ cultures, J. Physiol 252: 771–789.PubMedGoogle Scholar
  31. Berg, D. K., and Hall, Z. W., 1975b, Increased extrajunctional acetylcholine sensitivity produced by chronic post–synaptic neuromuscular blockage, J. Physiol 244: 659–676.Google Scholar
  32. 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: 147–151.PubMedGoogle Scholar
  33. Bevan, S., and Steinbach, J. H., 1977, The distribution of a–bungarotoxin binding sites on mammalian skeletal muscle developing in vivo, J. Physiol 267: 195–213.PubMedGoogle Scholar
  34. Birks, R., Katz, B., and Miledi, R., 1960, Physiological and structural changes at the amphibian myoneural junction in the course of nerve degeneration, J. Physiol 150: 145–168.PubMedGoogle Scholar
  35. Boheim, G., Hanke, W., Barrantes, F. J., Eibl, H., Sakmann, B., Fels, G., and Maelicke, A., 1981, Agonist–activated ionic channels in acetylcholine receptor reconstituted into planar lipid bilayers, Proc. Natl. Acad. Sci. USA 78: 3586–3590.PubMedGoogle Scholar
  36. Boulter, J., and Patrick, J., 1977, Purification of an acetylcholine receptor from a nonfusing muscle cell line, Biochemistry 16: 4900–4908.PubMedGoogle Scholar
  37. Boyd, N. D., and Cohen, J. B., 1980a, Kinetics of binding of [3H]–acetylcholine and 3[H]–carbamylcholine to Torpedo postsynaptic membranes: Slow conformational transitions of the cholinergic receptor, Biochemistry 19: 5344–5353.PubMedGoogle Scholar
  38. Boyd, N. D., and Cohen, J. B., 1980b, Kinetics of binding of [3H]–acetylcholine to Torpedo postsynaptic membranes: Association and dissociation rate constants by rapid mixing and ultrafiltration, Biochemistry 19: 5353–5358.PubMedGoogle Scholar
  39. Briley, M., and Changeux, J.-P., 1977, Isolation and purification of the nicotinic acetylcholine receptor and its functional reconstitution into a membrane environment, Int. Rev. Neurobiol 20: 31–59.PubMedGoogle Scholar
  40. Briley, M. S., and Changeux, J.-P., 1978, Recovery of some functional properties of the detergent–extracted cholinergic receptor protein from Torpedo marmorata after reintegration into a membrane environment, Eur. J. Biochem 84: 429–439.PubMedGoogle Scholar
  41. Brisson, A., Devaux, P. F., and Changeux, J. P., 1975, Effet anesthésique local de plusieurs composés liposolubles sur la réponse de l’électroplaque de Gymnote a la carbamylcholine et sur la liaison de l’acétylcholine au récepteur cholinergique de Torpille, C.R. Acad. Sci. (Paris) 280D: 2153–2156.Google Scholar
  42. Brockes, J. P., Berg, D. K., and Hall, Z. W., 1975, The biochemical properties and regulation of acetylcholine receptors in normal and denervated muscle, Cold Spring Harbor Symp. Quant. Biol 40: 253–262.Google Scholar
  43. Brown, D. R., and Taylor, P., 1983, The influence of antibiotics on agonist occupation and functional states of the nicotinic acetylcholine receptor, Mol. Pharmacol, 23: 8–16.PubMedGoogle Scholar
  44. Burden, S. J., 1982, Identification of an intracellular postsynaptic antigen at the frog neuromuscular junction, J. Cell Biol 94: 521–530.PubMedGoogle Scholar
  45. Burden, S. J., Sargent, P. B., and McMahan, U. J., 1979, Acetylcholine receptors in regenerating muscle accumulate at original sites in the absence of the nerve, J. Cell Biol 82: 412–425.PubMedGoogle Scholar
  46. Burgermeister, W., Catterall, W., and Witkop, B., 1977, Histrionicotoxin enhances agonist–induced desensitization of acetylcholine receptor, Proc. Natl. Acad. Sci. USA 74: 5754–5758.PubMedGoogle Scholar
  47. Cartaud, J., Benedetti, E., Sobel, A., and Changeux, J.–P., 1978, A morphological study of the cholinergic receptor protein from Torpedo marmorata in its membrane environment and in its detergent extracted purified form, J. Cell Sci 29: 313–337.PubMedGoogle Scholar
  48. Cartaud, J., Sobel, A., Rousselet, A., Devaux, P., and Changeux, J.–P., 1981, Consequences of alkaline treatment for the ultra–structure of the acetylcholine receptor–rich membranes from Torpedo marmorata electric organ, J. Cell Biol 90: 418–426.PubMedGoogle Scholar
  49. Cartaud, J., Oswald, R., Clément, G., and Changeux, J.–P., 1982, Evidence for a skeleton in acetylcholine receptor–rich membranes from Torpedo marmorata electric organ, FEBS Lett. 145: 250.Google Scholar
  50. Cash, D. J., Aoshima, H., and Hess, G. P., 1981, Acetylcholine–induced cation translocation across cell membranes and inactivation of the acetylcholine receptor: Chemical kinetic measurements in the millisecond time region, Proc. Natl. Acad. Sci. USA 78: 3318–3322.PubMedGoogle Scholar
  51. Catterall, W. A., 1975, Sodium transport by the acetylcholine receptor of cultured muscle cells, J. Biol. Chem 250: 1775–1781.Google Scholar
  52. Chang, H. W., and Bock, E., 1977, Molecular forms of the acetylcholine receptor. Effects of calcium ions and a sulthydryl reagent on the occurrence of oligomers, Biochemistry 16: 4513–4520.PubMedGoogle Scholar
  53. Chang, C. C., and Huang, M. C., 1975, Turnover of junctional and extrajunctional acetylcholine receptors of the rat diaphragm, Nature 253: 643–644.PubMedGoogle Scholar
  54. Chang, C. C., and Lee, C.–Y., 1963, Isolation of neurotoxins from the venom of Bungarus multicinctus and their modes of neuromuscular blocking action, Arch. Int. Pharmacodyn. Ther 144: 241–257.PubMedGoogle Scholar
  55. Changeux, J.-P., 1981, The acetylcholine receptor: An allosteric membrane protein, Harvey Lect. 75: 85–254.Google Scholar
  56. Changeux, J.-P., Heidmann, T., Popot, J., and Sobel, A., 1979, Reconstitution of a functional acetylcholine regulator under defined conditions, FEBS Lett. 105: 181–187.PubMedGoogle Scholar
  57. Clark, D. G., Macmurchie, D. D., Elliott, E., Wolcott, R. G., Landel, A. M., and Raftery, M. A., 1972, Elapid neurotoxins, purification, characterization, and immunochemical studies of a–bungarotoxin, Biochemistry 11: 1663–1668.PubMedGoogle Scholar
  58. Claudio, T., Ballivet, M., Patrick, J., and Heinemann, S., 1983, Torpedo californica acetylcholine receptor 60,000 dalton subunit p. nucleotide sequence of cloned cDNA, deduced amino acid sequence, subunit structural predictions, Proc. Natl. Acad. Sci. USA, 80: 111–115.Google Scholar
  59. Cohen, J. B., 1978, Ligand binding properties of membrane bound cholinergic receptors of Torpedo marmorata, in: Molecular Specialization and Symmetry in Membrane Function ( A. K. Solomon and M. Karnosky, eds.), Harvard University Press, Cambridge, Massachusetts, pp. 99–128.Google Scholar
  60. Colquhoun, D., and Sakmann, B., 1981, Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels, Nature 294: 464–466.PubMedGoogle Scholar
  61. Conti–Tronconi, B., Brigonzi, A., Fumagalli, G., Sher, M., Cosi, V., Piccolo, G., and Clementi, F., 1981a, Antibody–induced degradation of acetylcholine receptor in myasthenia gravis: Clinical correlates and pathogenetic significance, Neurology 31: 1440–1444.Google Scholar
  62. Conti–Tronconi, B., Tzartos, S., and Lindstrom, J., 1981b, Monoclonal antibodies as probes of acetylcholine receptor structure. II. Binding to native receptor, Biochemistry 20: 2181–2191.Google Scholar
  63. Conti–Tronconi, B. M., Hunkapiller, M. W., Lindstrom, J. M., and Raftery, M. A., 1982a, Subunit structure of the acetylcholine receptor from Electrophorus electricus, Proc. Natl. Acad. Sci. USA 79: 6489–6493.Google Scholar
  64. Conti-Tronconi, B. M., Hunkapiller, M. W., Lindstrom, J. M., and Raftery, M. A., 1982b, Amino acid sequence homology between a–subunits from Torpedo and Electrophorus acetylcholine receptor, Biochem. Biophys. Res. Commun 106: 312–318.PubMedGoogle Scholar
  65. Conti-Tronconi, B. M., Dunn, S. M. J., and Raftery, M. A., 1982c, Functional stability of Torpedo acetylcholine receptor. Effects of protease treatment, Biochemistry 21: 893–899.Google Scholar
  66. Conti-Tronconi, B. M., Dunn, S. M. J., and Raftery, M. A., 1982d, Independent sites of low and high affinity for agonists on Torpedo californica acetylcholine receptor, Biochem. Biophys. Res. Commun 107: 123–129.PubMedGoogle Scholar
  67. Conti-Tronconi, B. M., Gotti, C. M., Hunkapiller, M. W., and Raftery, M. A., 1982e, Mammalian muscle acetylcholine receptor: A supramolecular structure formed by four related proteins, Science 218: 1227–1229.PubMedGoogle Scholar
  68. Criado, M., and Barrantes, F. J., 1982, Effects of periodate oxidation and glycosidases on structural and functional properties of the acetylcholine receptor and the non–receptor, peripheral v–polypeptide (M, 43,000), Neurochem. Int, 4: 289–302.PubMedGoogle Scholar
  69. Criado, M., Eibl, H., and Barrantes, F. J., 1982, Effects of lipids on acetylcholine receptor. Essential need of cholesterol for maintenance of agonist–induced state transitions in lipid vesicles, Biochemistry 21: 3622–3629.Google Scholar
  70. Culver, P., Fenical, W., and Taylor, P., 1984, Lophotoxin irreversibly inactivates the nicotinic acetylcholine receptor by preferential association at one of the two primary agonist sties. J. Biol Chem 259: 3763–3770.PubMedGoogle Scholar
  71. Dale, H. H., 1934, Chemical transmission of the effects of nerve impulses, Br. Med. J 1: 835–841.PubMedGoogle Scholar
  72. Dalziel, A. W., Rollins, E. S., and McNamee, M. G., 1980, The effect of cholesterol on agonist–induced flux in reconstituted acetylcholine receptor vesicles, FEBS Lett. 122: 193–196.Google Scholar
  73. Damle, V. N., and Karlin, A., 1978, Affinity labeling of one of two a–neurotoxin binding sites in acetylcholine receptor from Torpedo californica, Biochemistry 17: 2039–2045.PubMedGoogle Scholar
  74. Damle, V. N., and Karlin, A., 1980, Effects of agonists and antagonists on the reactivity of the binding site disulfide in acetylcholine receptor from Torpedo californica, Biochemistry 19: 3924–3932.PubMedGoogle Scholar
  75. Damle, V. N., McLaughlin, M., and Karlin, A., 1978, Bromoacetylcholine as an affinity label of the acetylcholine receptor from Torpedo californica, Biochem. Biophys. Res. Commun 84: 845–851.PubMedGoogle Scholar
  76. Davis, C., Gordon, A., and Diamond, I., 1982, Specificity and localization of the acetylcholine receptor kinase, Proc. Natl. Acad. Sci. USA 79: 3666–3670.Google Scholar
  77. Del Castillo, J., and Katz, B., 1954, Quantal components of the endplate potential, J. Physiol 124: 560–573.Google Scholar
  78. Del Castillo, J., and Katz, B., 1954, Quantal components of the endplate potential, J. Physiol 124: 560573.Google Scholar
  79. Dennis, M. J., Ziskind–Conhaim, L., and Harris, A. J., 1981, Development of neuromuscular junctions in rat embryos, Dey. Biol 81: 266–279.Google Scholar
  80. DevillersThiery, A., Changeux, J.P., Paroutaud, P., and Strosberg, A., 1979, The aminoterminal sequence of the 40,000 molecular weight subunit of the acetylcholine receptor protein from Torpedo marmorata, FEBS Lett. 104: 99–105.Google Scholar
  81. DevillersThiery, A., Giraudat, J., Bentaboulet, M., and Changeux, J.–P., 1983, Complete mRNA coding sequence of the acetylcholine binding subunit of Torpedo marmorata acetylcholine receptor: A model for the transmembrane organization of the polypeptide chain. Proc. Natl. Acad. Sci. USA 80: 2067–2071.Google Scholar
  82. Devreotes, P. N., and Fambrough, D. M., 1975, Acetylcholine receptor turnover in membranes of developing muscle fibers, J. Cell Biol 65: 335–358.PubMedGoogle Scholar
  83. Devreotes, P. N., and Fambrough, D. M., 1976, Turnover of acetylcholine receptors in skeletal muscle, Cold Spring Harbor Symp. Quant. Biol 40: 237–251.PubMedGoogle Scholar
  84. Diamond, J., and Miledi, R., 1962, A study of foetal and newborn rat muscle fibres, J. Physiol 162: 393–408.PubMedGoogle Scholar
  85. Dionne, V. E., Steinbach, J. H., and Stevens, C. F., 1978, An analysis of the dose—response relationship of voltage–clamped frog neuromuscular junctions, J. Physiol 281: 421–444.PubMedGoogle Scholar
  86. Drachman, D. B., 1981, The biology of myasthenia gravis, Annu. Rev. Neurosci 4: 195–225.PubMedGoogle Scholar
  87. Drachman, D. B., Adams, R., Josifek, L., and Self, S., 1982, Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis, New Eng. J. Med 307: 769–775.PubMedGoogle Scholar
  88. Dreyer, F., Peper, K., and Sterz, R., 1978, Determination of dose—response curves by quantitative ionophoresis at the frog neuromuscular junction, J. Physiol 281: 395–419.PubMedGoogle Scholar
  89. Dunn, S. J. M., and Raftery, M. A., 1982, Activation and desensitization of Torpedo acetylcholine receptor: Evidence for separate binding sites. Proc. Natl. Acad. Sci. USA 79: 6757–6761.PubMedGoogle Scholar
  90. Dunn, M. J., Blanchard, S. G., and Raftery, M. A., 1981, Effects of local anesthetics and histrionicotoxin on the binding of carbamoylcholine to membrane—bound acetylcholine receptor, Biochemistry 20:5617–5624.Google Scholar
  91. Dwyer, T. M., Adams, D., and Hille, B., 1980, The permeability of the endplate–channel to organic cations in frog muscle, J. Gen. Physiol 75: 469–492.PubMedGoogle Scholar
  92. Einarson, B., Gullick, W., Conti–Tronconi, B., and Lindstrom, J., 1982, Subunit composition of fetal calf muscle nicotinic acetylcholine receptor, Biochemistry 21: 5295–5302.Google Scholar
  93. Eldefrawi, A. T., Eldefrawi, M. E., Albuquerque, E. X., Oliveira, A. C., Mansour, N., Adler, M., Daly, J. W., Brown, G. G., Burgermeister, W., and Witkop, B., 1977, Perhydrohistrionicotoxin: A potential ligand for the ion conductance modulator of the acetylcholine receptor, Proc. Natl. Acad. Sci. USA 74: 2172–2176.PubMedGoogle Scholar
  94. Eldefrawi, M. E., Eldefrawi, A. T., Mansour, N. A., Daly, J. W., Witkop, B., and Albuquerque, E. X., 1978, Acetylcholine receptor and ionic channel of Torpedo electroplax: Binding of perhydrohistrionicotoxin to membrane and solubilized preparations, Biochemistry 17: 5474–5484.PubMedGoogle Scholar
  95. Eldefrawi, M. E., Aronstam, R. S., Bakry, N. M., Eldefrawi, A. T., and Albuquerque, E. X., 1980, Activation, inactivation, and desensitization of acetylcholine receptor channel complex detected by binding of perhydrohistrionicotoxin, Proc. Natl. Acad. Sci. USA 77: 2309–2313.PubMedGoogle Scholar
  96. Elliott, J., and Raftery, M. A., 1977, Interactions of perhydrohistrionicotoxin with postsynaptic membranes, Biochem. Biophys. Res. Commun 77: 1347–1353.Google Scholar
  97. Elliott, J., Dunn, S. M. J., Blanchard, S. G., and Raftery, M. A., 1979, Specific binding of perhydrohistrionicotoxin to Torpedo acetylcholine receptor, Proc. Natl. Acad. Sci. USA 76: 2576–2579.PubMedGoogle Scholar
  98. Engel, A. G., Tsujihata, M., Lindstrom, J., and Lennon, V., 1976, The motor end–plate in myastheniaGoogle Scholar
  99. gravis and in experimental autoimmune myasthenia gravis. A quantitative ultrastructural study, Ann. N.Y. Acad. Sci 274: 60–79.Google Scholar
  100. Engel, A. G., Lindstrom, J. M., Lambert, E. H., and Lennon, V. A., 1977a, Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and its experimental autoimmune model, Neurology 27: 307–315.PubMedGoogle Scholar
  101. Engel, A., Lambert, E. M., and Howard, G., 1977b, Localization of acetylcholine receptors, antibodies, and complement at endplates of patients with myasthenia gravis, Mayo Clin. Proc 52: 267–280.PubMedGoogle Scholar
  102. Engel, A. G., Sakakibara, H., Sahashi, K., Lindstrom, J. M., Lambert, E. M., and Lennon, V. A., 1979, Passively transferred experimental autoimmune myasthenia gravis, Neurology 29: 179–188.Google Scholar
  103. Epstein, M., and Racker, E., 1978, Reconstitution of carbamylcholine–dependent sodium ion flux and desensitization of the acetylcholine receptor from Torpedo californica, J. Biol. Chem 253: 6660–6662.PubMedGoogle Scholar
  104. Fairclough, R. H., Finer–Moore, J., Love, R. A., Kristofferson, D., Desmeules, P. J. and Stroud, R. M., 1984, Subunit organization and structure of an acetylcholine receptor. Cold Spring Harbor Symposia 48.Molecular Neurobiology,in press.Google Scholar
  105. Fambrough, D. M., 1979, Control of acetylcholine receptors in skeletal muscle, Physiol. Rev 59: 165–227.PubMedGoogle Scholar
  106. Fambrough, D. M., and Devreotes, P. N., 1978, Newly synthesized acetylcholine receptors are located in the Golgi apparatus, J. Cell Biol 76: 237–244.PubMedGoogle Scholar
  107. Fambrough, D. M., Bayne, E. K., Gardner, J. M., Anderson, M. J., Wakshull, E., and Rotundo, R. L., 1982, Monoclonal antibodies to skeletal muscle cell surface, in: Neuroimmunology ( J. Brockes, ed.), Plenum, New York, pp. 49–89.Google Scholar
  108. Fatt, P., and Katz, B., 1951, An analysis of the end–plate potential recorded with an intra–cellular electrode, J. Physiol 115:320–370.PubMedGoogle Scholar
  109. Feltz, A., and Trautmann, A., 1982, Desensitization at the frog neuromuscular junction: A biphasic process, J. Physiol 322: 257–272.PubMedGoogle Scholar
  110. Fertuck, H. C., and Salpeter, M. M., 1974, Localization of 125I–labeled a–bungarotoxin binding at mouse motor endplates, Proc. Natl. Acad. Sci. USA 71: 1376–1378.PubMedGoogle Scholar
  111. Fertuck, H. C., and Salpeter, M. M., 1976, Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after 1251–abungarotoxin binding at mouse neuromuscular junctions, J. Cell Biol 69: 144–158.PubMedGoogle Scholar
  112. Flynn, D. D., Kloog, Y., Potter, L. T., and Axelrod, J., 1982, Enzymatic methylation of the membrane–bound nicotinic acetylcholine receptor, J. Biol. Chem 257: 9513–9517.PubMedGoogle Scholar
  113. Fox, G. O., and Richardson, G. P., 1979, The developmental morphology of Torpedo marmorata: Electric organ—Electrogenic phase, J. Comp. Neurol 185: 293–316.PubMedGoogle Scholar
  114. Frank, E., and Fischbach, G. D., 1979, Early events in neuromuscular junction formation in vitro: Induction of acetylcholine receptor clusters in the postsynaptic membrane and morphology of newly formed synapses, J. Cell Biol 83: 143–158.PubMedGoogle Scholar
  115. Froehner, S. C., 1981, Identification of exposed and buried determinants of the membrane–bound acetylcholine receptor from Torpedo californica, Biochemistry 20: 4905–4915.PubMedGoogle Scholar
  116. Froehner, S. C., Karlin, A., and Hall, Z. W., 1977a, Affinity alkylation labels two subunits of reduced acetylcholine receptor from mammalian muscle, Proc. Natl. Acad. Sci. USA 74: 4685–4688.PubMedGoogle Scholar
  117. Froehner, S. C., Reiness, C. G., and Hall, Z. W., 1977b, Subunit structure of the acetylcholine receptor from denervated rat skeletal muscle, J. Biol. Chem 252: 8589–8596.Google Scholar
  118. Froehner, S. C., Gulbrandsen, V., Hyman, C., Jeng, A. Y., Neubig, R. R., and Cohen, J. B., 1981, Immunofluorescence localization at the mammalian neuromuscular junction of the M r 43,000 protein of Torpedo postsynaptic membranes, Proc. Natl. Acad. Sci. USA 78: 5230–5234.PubMedGoogle Scholar
  119. Froehner, S. C., Wray, B. E., and Sealock, R., 1983, Ultrastructural localization of 43K protein in Torpedo postsynaptic membranes with monoclonal antibodies, Soc. for Neurosci. Abstr, 168. 5, p. 578.Google Scholar
  120. Fumagalli, G., Engel, A., and Lindstrom, J., 1982a, Ultrastructural aspects of acetylcholine receptor turnover at the normal end–plate and in autoimmune myasthenia gravis, J. Neuropathol. Exp. Neurol 41: 567–579.PubMedGoogle Scholar
  121. Fumagalli, G., Engel, A. G., and Lindstrom, J., 1982b, Estimation of acetylcholine receptor degradation rate by external gamma counting in vivo, Mayo Clin. Proc, 57: 758–764.PubMedGoogle Scholar
  122. Gage, P. W., McBurney, R. N., and Schneider, G. T., 1975, Effects of some aliphatic alcohols on the conductance change caused by a quantum of acetylcholine at the toad end–plate, J. Physiol 244: 409–429.PubMedGoogle Scholar
  123. Gardner, J. M., and Fambrough, D. M., 1979, Acetylcholine receptor degradation measured by density labeling: Effects of cholinergic ligands and evidence against recycling, Cell 16: 661–674.PubMedGoogle Scholar
  124. Gershoni, J. M., Palade, G. E., Hawrot, E., Klimowicz, D. W., and Lentz, T. L., 1982, Analysis of a bungarotoxin binding to Torpedo acetylcholine receptor by electrophoretic transfer techniques, J. Cell Biol 95: 422a.Google Scholar
  125. Giraudat, J., Devillers–Thiery, A., Auffray, C., Rougeon, F., and Changeux, J. P., 1982, Identification of a cDNA clone coding for the acetylcholine binding subunit of Torpedo marmorata acetylcholine receptor, EMBO J. 1: 713–717.PubMedGoogle Scholar
  126. Gomez, C., Richman, D., Berman, P., Burres, S., Amason, B., and Fitch, F., 1979, Monoclonal antibodies against purified nicotinic acetylcholine receptor, Biochem. Biophys. Res. Commun 88: 575–582.PubMedGoogle Scholar
  127. Gonzalez–Ros, J. M., Paraschos, A., and Martinez–Carrion, M., 1980, Reconstitution of functional membrane–bound acetylcholine receptor from isolated Torpedo californica receptor protein and electroplax lipids, Proc. Natl. Acad. Sci. USA 77: 1796–1800.Google Scholar
  128. Gonzalez–Ros, J. M., Llanillo, M., Paraschos, A., and Martinez–Carrion, M., 1982, Lipid environment of acetylcholine receptor from Torpedo californica, Biochemistry 21: 3467–3474.Google Scholar
  129. Gordon, A. S., Davis, C. G., and Diamond, I., 1977a, Phosphorylation of membrane proteins at a cholinergic synapse, Proc. Natl. Acad. Sci. USA 74: 263–267.PubMedGoogle Scholar
  130. Gordon, A. S., Davis, C. G., Milfay, D., and Diamond, I., 1977b, Phosphorylation of acetylcholine receptor by endogenous membrane protein kinase in receptor–enriched membranes of Torpedo californica, Nature 267: 539–540.PubMedGoogle Scholar
  131. Gordon, A. S., Milfay, D., Davis, C. G., and Diamond, I., 1979, Protein phosphatase activity in acetylcholine receptor–enriched membranes, Biochem Biophys. Res. Commun 87: 876–883.PubMedGoogle Scholar
  132. Gordon, A. S., Davis, C. G., Milfay, D., Kaur, J., and Diamond, I., 1980, Membrane–bound protein kinase activity in acetylcholine receptor–enriched membranes, Biochim. Biophys. Acta 600: 421–431.PubMedGoogle Scholar
  133. Gotti, C., Conti–Tronconi, B. M., and Raftery, M. A., 1982, Mammalian muscle acetylcholine receptor purification and characterization, Biochemistry 21: 3148–3154.Google Scholar
  134. Grunhagen, H. H., Iwatsubo, M., and Changeux, J.-P., 1977, Fast kinetic studies on the interaction of cholinergic agonists with the membrane–bound acetylcholine receptor from Torpedo marmorata as revealed by quinacrine fluorescence, Eur. J. Biochem 80: 225–242.PubMedGoogle Scholar
  135. Gullick, W. J., and Lindstrom, J. M., 1982a, The antigenic structure of the acetylcholine receptor from Torpedo californica, J. Cell. Biochem, 19: 223–230.PubMedGoogle Scholar
  136. Gullick, W. J., and Lindstrom, J. M., 1982b, Structural similarities between acetylcholine receptors from fish electric organs and mammalian muscle, Biochemistry, 21: 4563–4569.PubMedGoogle Scholar
  137. Gullick, W. J., and Lindstrom, J. M., 1983a, Mapping the binding of monoclonal antibodies to the acetylcholine receptor from Torpedo californica, Biochemistry 22: 3312–3320.Google Scholar
  138. Gullick, W. J., and Lindstrom, J. M., 1983b, Comparison of the subunit structure of acetylcholine receptors from muscle and electric organ of Electrophorus electricus, Biochemistry 22: 380l–3807.Google Scholar
  139. Gullick, W. J., Tzartos, S., and Lindstrom, J., 1981, Monoclonal antibodies as probes of acetylcholine receptor structure. I. Peptide mapping, Biochemistry 20: 2173–2180.PubMedGoogle Scholar
  140. Guy, H. R., 1984, A structural model of the acetylcholine receptor channel based on partition energy and helix packing calculations. Biophys. J, 45: 249–261.PubMedGoogle Scholar
  141. Gysin, R., Wirth, M., and Flanagan, S. D., 1981, Structural heterogeneity and subcellular distribution of nicotinic synapse–associated proteins, J. Biol. Chem 256: 11373–11376.PubMedGoogle Scholar
  142. Haggerty, J. G., and Froehner, S. C., 1981, Restoration of 125I–a–Bungarotoxin binding activity to the a–subunit of Torpedo acetylcholine receptor isolated by gel electrophoresis in sodium dodecyl sulfate, J. Biol. Chem 256: 8294–8297.PubMedGoogle Scholar
  143. Hall, Z. W., Lubit, B. W., and Schwartz, J. H., 1981, Cytoplasmic actin in postsynaptic structures at the neuromuscular junction, J. Cell Biol 90: 789–792.PubMedGoogle Scholar
  144. Hamill, O. P., and Sakmann, B., 1981, Multiple conductance states of single acetylcholine receptor channels in embryonic muscle cells, Nature 294: 462–464.PubMedGoogle Scholar
  145. Hamilton, S. L., McLaughlin, M., and Karlin, A., 1979, Formation of disulfide–linked oligomers of acetylcholine receptor in membrane from Torpedo electric tissue, Biochemistry 18: 155–163.PubMedGoogle Scholar
  146. Hanover, J A., and Lennarz, W. J., 1981, Transmembrane assembly of membrane and secretory glycol proteins, Arch. Biochem. Biophys 211:1–19.Google Scholar
  147. Hartzell, H. C., 1982, Physiological consequences of muscarinic receptor activation, Trends Pharmacol. Sci 4: 213–214.Google Scholar
  148. Hartzell, H. C., and Fambrough, D. M., 1972, Acetylcholine receptors. Distribution and extrajunctional density in rat diaphragm after denervation correlated with acetylcholine sensitivity, J. Gen. Physiol 60: 248–262.PubMedGoogle Scholar
  149. Hartzell, H. C., and Fambrough, D. M., 1973, Acetylcholine receptor production and incorporation into plasma membranes of developing muscle fibers, Dey. Biol 30: 153–165.Google Scholar
  150. Hazelbauer, G. L., and Changeux, J.–P., 1974, Reconstitution of a chemically excitable membrane, Proc. Natl. Acad. Sci. USA 71: 1479–1483.PubMedGoogle Scholar
  151. Heidmann, T., and Changeux, J.–P., 1979a, Fast kinetic studies on the interaction of a fluorescent agonist with the membrane–bound acetylcholine receptor from Torpedo marmorata, Eur. J. Biochem 94: 255–279.PubMedGoogle Scholar
  152. Heidmann, T., and Changeux, J.-P., 1979b, Fast kinetic studies on the allosteric interactions between acetylcholine receptor and local anesthetic binding sites, Eur. J. Biochem 94: 281–296.PubMedGoogle Scholar
  153. Heidmann, T., and Changeux, J.-P., 1980, Interaction of a fluorescent agonist with the membrane–bound acetylcholine receptor from Torpedo marmorata in the millisecond time range: Resolution of an intermediate conformational transition and evidence for positive cooperative effects, Biochem. Biophys. Res. Commun 97: 889–896.PubMedGoogle Scholar
  154. Heidmann, T., and Changeux, J.-P., 1981, Stabilization of the high affinity state of the membrane–bound acetylcholine receptor from Torpedo marmorata by noncompetitive blockers. Evidence for dual interaction and pharmacological selectivity, FEBS Lett. 131: 239–244.PubMedGoogle Scholar
  155. Heidmann, T., Sobel, A., and Changeux, J.–P., 1980a, Conservation of the kinetic and allosteric properties of the acetylcholine receptor in its Na–cholate soluble 9S form: Effect of lipids, Biochem. Biophys. Res. Commun 93: 127–133.PubMedGoogle Scholar
  156. Heidmann, T., Sobel, A., Popot, J.–L., and Changeux, J.–P., 1980b, Reconstitution of a functional acetylcholine receptor: Conservation of the conformational and allosteric transitions and recovery of the permeability response: Role of lipids, Eur. J. Biochem 110: 35–55.PubMedGoogle Scholar
  157. Heidmann, T., Cuisinier, J. B., and Changeux, J.–P., 1981, Conservation des propriétés allostériques de la protéine réceptrice de l’acétylcholine en solution détergente sans addition de lipides, C. R. Acad. Sci. (Paris) 292 (série III): 13–15.Google Scholar
  158. Heinemann, S., Bevan, S., Kullberg, R., Lindstrom, J., and Rice, J., 1977, Modulation of the acetylcholine receptor by anti–receptor antibody, Proc. Natl. Acad. Sci. USA 74: 3090–3094.PubMedGoogle Scholar
  159. Heinemann, S., Merlie, J., and Lindstrom, J., 1978, Modulation of acetylcholine receptor in rat diaphragm by antireceptor sera, Nature 274: 65–68.PubMedGoogle Scholar
  160. Hess, G. P., Pasquale, E. B., Walker, J. W., and McNamee, M. G., 1982, Comparison of acetylcholine receptor–controlled cation flux in membrane vesicles from Torpedo californica and Electrophorus electricus: Chemical kinetic measurements in the millisecond region, Proc. Natl. Acad. Sci. USA 79: 963–967.PubMedGoogle Scholar
  161. Heuser, J. E., and Salpeter, S. R., 1979, Organization of acetylcholine receptors in quick–frozen, deep–etched, and rotary–replicated Torpedo postsynaptic membrane, J. Cell Biol 82: 150–173.PubMedGoogle Scholar
  162. Heuser, J. E., Reese, T. S., Dennis, M. J., Jan, Y., Jan, L., and Evans, L., 1979, Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release, J. Cell Biol 81: 275–300.PubMedGoogle Scholar
  163. Holtzman, E., Wise, D., Wall, J., and Karlin, A., 1982, Electron microscopy of complexes of isolated acetylcholine receptor, biotinyl–toxin, and avidin, Proc. Natl. Acad. Sci. USA 79: 310–314.PubMedGoogle Scholar
  164. Horn, R., and Patlak, J., 1980, Single channel currents from excised patches of muscle membrane, Proc. Natl. Acad. Sci. USA 77: 6930–6934.PubMedGoogle Scholar
  165. Huang, L. M., Catterall, W. A., and Ehrenstein, G., 1978, Selectivity of cations and nonelectrolytes for acetylcholine–activated channels in cultured muscle cells, J. Gen. Physiol 71: 397–410.PubMedGoogle Scholar
  166. Hucho, F., Bandini, G., and Sûarez–Isla, B. A., 1978, The acetylcholine receptor as part of a protein complex in receptor–enriched membrane fragments from Torpedo californica electric tissue, Eur. J. Biochem 83: 335–340.PubMedGoogle Scholar
  167. Huganir, R. L., and Greengard, P., 1983, cAMP–dependent protein kinase phosphorylates the nicotinic acetylcholine receptor, Proc. Natl. Acad. Sci. USA 80: 1130–1134.Google Scholar
  168. Huganir, R. L., and Racker, E., 1980, Endogenous and exogenous proteolysis of the acetylcholine receptor from Torpedo californica, J. Supramol. Struct 14: 215–221.Google Scholar
  169. Huganir, R. L., Schell, M. A., and Racker, E., 1979, Reconstitution of the purified acetylcholine receptor from Torpedo californica, FEBS Lett. 108: 155–160.PubMedGoogle Scholar
  170. Huganir, R. L., Coronado, R., Silverman, D. H., and Racker, E., 1981, Structure and function of the nicotinic acetylcholine receptor, Abstracts, VII Internat!. Biophys. Congress and III Pan American Biochem. Congress, Mexico City, Mexico, p. 258.Google Scholar
  171. James, R. W., Kato, A. C., Rey, M.–J., and Fulpius, B. W., 1980, Monoclonal antibodies directed against the neurotransmitter binding site of nicotinic acetylcholine receptor, FEBS Lett. 120: 145–148.PubMedGoogle Scholar
  172. Jenkinson, D. H., 1960, The antagonism between tubocurarine and substances which depolarize the motor end–plate, J. Physiol 152: 309–324.Google Scholar
  173. Jenkinson, D. M., and Nicholls, J. G., 1961, Contracture and permeability changes produced by acetylcholine in depolarized denervated muscle, J. Physiol 159: 111–127.PubMedGoogle Scholar
  174. Kaldany, R. R. J., and Karlin, A., 1983, Reaction of quinacrine mustard with the acetylcholine receptor from Torpedo californica. Functional consequences and sites of labeling, J. Biol. Chem 258: 6232–6242.PubMedGoogle Scholar
  175. Kao, I., and Drachman, D. B., 1977, Myasthenic immunoglobulin accelerates acetylcholine receptor degradation, Science 196: 527–529.PubMedGoogle Scholar
  176. Karlin, A., 1980, Molecular properties of nicotinic acetylcholine receptors, in: The Cell Surface and Neuronal Function ( G. Poste, G. Nicolson, and C. Cotman, eds.), Elsevier/North–Holland Biomedical Press, New York, pp. 191–260.Google Scholar
  177. Karlin, A., Weill, C. L., McNamee, M. G., and Valderrama, R., 1975, Facets of the structures of acetylcholine receptors from Electrophorus and Torpedo, Cold Spring Harbor Symp. Quant. Biol 40: 203–210.Google Scholar
  178. Karlsson, E., Arnberg, H., and Eaker, D., 1971, Isolation of the principal neurotoxins of two Naja naja subspecies, Eur. J. Biochem 21: 1–16.PubMedGoogle Scholar
  179. Karpen, J. W., Aoshima, H., Abood, L. G., and Hess, G. P., 1982, Cocaine and phencyclidine inhibition of the acetylcholine receptor: Analysis of the mechanisms of action based on measurements of ion flux in the millisecond–to–minute time region, Proc. Natl. Acad. Sci. USA 79: 2509–2513.PubMedGoogle Scholar
  180. Kato, G., and Changeux, J.–P., 1976, Studies on the effect of histrionicotoxin on the monocellular electroplax from Electrophorus electricus and on the binding of 3H–acetylcholine to membrane fragments from Torpedo marmorata, Mol. Pharmacol 12: 92–100.PubMedGoogle Scholar
  181. Katz, B., 1966, Nerve, Muscle and Synapse, McGraw–Hill, New York.Google Scholar
  182. Katz, B., and Miledi, R., 1965, The measurement of synaptic delay, and the time course of acetylcholine release at the neuromuscular junction, Proc. Roy. Soc. (London) B 161: 483–496.Google Scholar
  183. Katz, B., and Miledi, R., 1972, The statistical nature of the acetylcholine potential and its molecular components, J. Physiol 224: 665–699.PubMedGoogle Scholar
  184. Katz, B., and Miledi, R., 1975, The effect of procaine on the action of acetylcholine at the neuromuscular junction, J. Physiol 249: 269–284.PubMedGoogle Scholar
  185. Katz, B., and Miledi, R., 1977, Transmitter leakage from motor nerve endings, Proc. Roy. Soc. (London) B 196: 59–72.Google Scholar
  186. Katz, B., and Miledi, R., 1978, A re–examination of curare action at the motor endplate, Proc. Roy. Soc. (London) B 203: 119–133.Google Scholar
  187. Katz, B., and Thesleff, S., 1957, A study of the desensitization produced by acetylcholine at the motor end–plate, J. Physiol 138: 63–80.PubMedGoogle Scholar
  188. Kemp, G., Morley, B., Dwyer, D., and Bradley, R. J., 1980, Purification and characterization of nicotinic acetylcholine receptors from muscle, Memb. Biochem 3: 229–257.Google Scholar
  189. Kilian, P. L., Dunlap, C. R., Mueller, P., Schell, M. A., Huganir, R. L., and Racker, E., 1980, Reconstitution of acetylcholine receptor from Torpedo californica with highly purified phospholipids: Effects of a–tocopherol, phylloquinone, and other terpenoid quinones, Biochem. Biophys. Res. Commun 93: 409–414.PubMedGoogle Scholar
  190. Kistler, J., and Stroud, R. M., 1981, Crystalline arrays of membrane–bound acetylcholine receptor, Proc. Natl. Acad. Sci. USA 78: 3678–3682.PubMedGoogle Scholar
  191. Kistler, J., Stroud, R. M., Klymkowsky, M. W., Lalancette, R. A., and Fairclough, R. H., 1982, Structure and function of an acetylcholine receptor, Biophys. J 37: 371–383.PubMedGoogle Scholar
  192. Kloog, Y., Flynn, D., Hoffman, A. R., and Axelrod, J., 1980, Enzymatic carboxymethylation of the nicotinic acetylcholine receptor, Biochem. Biophys. Res. Commun 97: 1474–1480.PubMedGoogle Scholar
  193. Klymkowsky, M. W., and Stroud, R. M., 1979, Immunospecific identification and three–dimensional structure of membrane–bound acetylcholine receptor from Torpedo californica, J. Mol. Biol 128: 319–334PubMedGoogle Scholar
  194. Klymkowsky, M. W., Heuser, J. E., and Stroud, R. M., 1980, Protease effects on the structure of acetylcholine receptor membranes from Torpedo californica, J. Cell Biol 85: 823–838.PubMedGoogle Scholar
  195. Koblin, D. D., and Lester, H. A., 1979, Voltage–dependent and voltage–independent blockade of acetyl choline receptors by local anesthetics in Electrophorus electroplaques, Mol. Pharmacol 15: 559–580PubMedGoogle Scholar
  196. Kordas, M., 1970, The effect of procaine on neuromuscular transmission, J. Physiol 209: 689–699PubMedGoogle Scholar
  197. Krenz, W.–D., Tashiro, T., Waechtler, K., Whittaker, V. P., and Witzemann, V., 1980, Aspects of the chemical embryology of the electromotor system of Torpedo marmorata with special reference to synaptogenesis, Neuroscience 5: 617–624.Google Scholar
  198. Krodel, E. K., Beckman, R. A., and Cohen, J. B., 1979, Identification of a local anesthetic binding site on postsynaptic membranes isolated from Torpedo marmorata electric tissue, Mol. Pharmacol 15: 294–312.PubMedGoogle Scholar
  199. Kuffier, S. W., and Yoshikami, D., 1975, The number of transmitter molecules in a quantum, J. Physiol 251: 465–482.Google Scholar
  200. Labarca, P., Lindstrom, J., and Montai, M., 1981, Channel properties of the purified acetylcholine receptor (AChR) in planar lipid bilayers, Abstracts, VII International Biophys. Congress and Ill Pan–American Biochem. Congress, Mexico City, Mexico, p. 258.Google Scholar
  201. Labarca, P., Lindstrom, J., and Montai, M., 1982, Studies on the properties of the purified acetylcholine receptor reconstituted in planar lipid bilayers, Biophys. J 37: 170a.Google Scholar
  202. Labarca, P., Lindstrom, J., and Montai, M., 1984a, Two kinetically coupled open states of the acetylcholine receptor channel, J. Neurosci 4: 502–507.PubMedGoogle Scholar
  203. Labarca, P., Lindstrom, J. and Montai, M 1984b, Acetylcholine receptor in planar lipid bilayers. Characterization of the channel properties of the purified nicotinic acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayers, J. Gen. Physiol 83.Google Scholar
  204. Lecar, H., Morris, E. C., and Wong, B. S., 1982, Single channel recording of weak cholinergic agonists, Biophys. J. 37: 313a.Google Scholar
  205. Lee, C. Y., 1970, Elapid neurotoxins and their mode of action, Clin. Toxicol 3: 457–472.PubMedGoogle Scholar
  206. Lee, T., Witzemann, V., Schimerlik, M., and Raftery, M. A., 1977, Cholinergic ligand induced affinity changes in Torpedo californica acetylcholine receptor, Arch. Biochem. Biophys 183: 57–63PubMedGoogle Scholar
  207. Lennon, V. A., Thompson, M., and Chen, J., 1980, Properties of nicotinic acetylcholine receptors isolated by affinity chromatography on monoclonal antibodies, J. Biol. Chem 255: 4395–4398.PubMedGoogle Scholar
  208. Lewis, C. A., 1979, Ion–concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction, J. Physiol. 286: 417–445.PubMedGoogle Scholar
  209. Libby, P., Bursztajn, S., and Goldberg, A. L., 1980, Degradation of the acetylcholine receptor in culturedmuscle cells: Selective inhibitors and the fate of undegraded receptors, Cell 19: 481–491.PubMedGoogle Scholar
  210. Linden, D., and Fambrough, D., 1979, Biosynthesis and degradation of acetylcholine receptors in rat skeletal muscles. Effects of electrical stimulation, Neuroscience 4: 527–538.PubMedGoogle Scholar
  211. Lindstrom, J. M., 1978, Biochemical studies of receptors: Solubilization, purification, characterization and studies with antibodies, in: Neurotransmitter Receptor Binding ( H. I. Yamamura, S. J. Enna, and M. J. Kuhar, eds.), Raven Press, New York, pp. 91–111.Google Scholar
  212. Lindstrom, J., 1979, Autoimmune response to acetylcholine receptor in myasthenia gravis and its animal model, Adv. Immunol 27: 50.Google Scholar
  213. Lindstrom, J., 1984, Acetylcholine receptors: Structure, function, synthesis, destruction and antigenicity, in: Myology,Chap. 27 (A. Engel and B. Banker.), McGraw—Hill, New York, in press.Google Scholar
  214. Lindstrom, J., and Einarson, B., 1979, Antigenic modulation and receptor loss in EAMG, Muscle Nerve 2: 173–179.PubMedGoogle Scholar
  215. Lindstrom, J., and Engel, A., 1981, Myasthenia gravis and the nicotinic cholinergic receptor, in: Receptor Regulation, Ser. B, Vol. 13, Chapman and Hall, London, pp. 161–214.Google Scholar
  216. Lindstrom, J. M., and Lambert, E. H., 1978, Content of acetylcholine receptor and antibodies bound to receptor in myasthenia gravis, experimental autoimmune myasthenia gravis and in Eaton–Lambert Syndrome, Neurology 28: 130–138.PubMedGoogle Scholar
  217. Lindstrom, J., and Patrick, J., 1974 Purification of the acetylcholine receptor by affinity chromatography, in: Synaptic Transmission and Neuronal Interaction, 26th Annual Meeting, Soc. Gen. Physiologists, Woods Hole, Massachusetts, September 1972 ( M. V. L. Bennett, ed.), Raven Press, New York, pp. 191–216.Google Scholar
  218. Lindstrom, J., Einarson, B., and Merlie, J., 1978, Immunization of rats with polypeptide chains from Torpedo acetylcholine receptor causes an autoimmune response to receptors in rat muscle, Proc. Natl. Acad. Sci. USA 75: 769–773.PubMedGoogle Scholar
  219. Lindstrom, J., Merlie, J., and Yogeeswaran, G., 1979a, Biochemical properties of acetylcholine receptor subunits from Torpedo californica, Biochemistry 18: 4465–4470.PubMedGoogle Scholar
  220. Lindstrom, J., Walter, B., and Einarson, B., 1979b, Immunochemical similarities between subunits of acetylcholine receptors from Torpedo, Electrophorus and mammalian muscle, Biochemistry 18:4470– 1480.Google Scholar
  221. Lindstrom, J., Gullick, W. J., Conti–Tronconi, B., and Ellisman, M., 1980a, Proteolytic nicking of the acetylcholine receptor, Biochemistry 19: 4791–4795.Google Scholar
  222. Lindstrom, J., Cooper, J., and Tzartos, S., 1980b, Acetylcholine receptors from Torpedo and Electrophorus have similar subunit structures, Biochemistry 19: 1454–1458.PubMedGoogle Scholar
  223. Lindstrom, J., Anholt, R., Einarson, B., Engel, A., Osame, M., and Montai, M., 1980c, Purification of acetylcholine receptors, reconstitution into lipid vesicles, and study of agonist–induced cation channel regulation, J. Biol. Chem 255: 8340–8350.PubMedGoogle Scholar
  224. Lindstrom, J., Einarson, B., and Tzartos, S., 1981a, Production and assay of antibodies to acetylcholine receptors, Meth. Enzymol 74: 432–460.PubMedGoogle Scholar
  225. Lindstrom, J., Tzartos, S., and Gullick, W., 1981b, Structure and function of acetylcholine receptors studied using monoclonal antibodies, Ann. N.Y. Acad. Sci 377: 1–19.PubMedGoogle Scholar
  226. Lindstrom, J. M., Cooper, J. F., and Swanson, L. W., 1983, Purification of acetylcholine receptors from the muscle of Electrophorus electricus, Biochemistry 22: 3796–3800.PubMedGoogle Scholar
  227. Lo, M. M. S., Garland, P. B., Lamprecht, J., and Barnard, E. A., 1980, Rotational mobility of the membrane–bound acetylcholine receptor of Torpedo electric organ measured by phosphorescence depolarization, FEBS Lett. 111: 407–412.PubMedGoogle Scholar
  228. Lo, M. M. S., Dolly, O. J., and Barnard, E. A., 1981, Molecular forms of the acetylcholine receptor from vertebrate muscles and Torpedo electric organ: Interactions with specific ligands, Eur. J. Biochem 116: 155–163.PubMedGoogle Scholar
  229. Loewi, 0., 1921, Über humorale übertragbarkeit der Herznervenwirkung, Pfluegers Arch. Ges. Physiol 189: 239–242.Google Scholar
  230. Magazanik, L. G., and Vyskocil, F., 1970, Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and on the ionic changes in the medium, J. Physiol 210: 507–518.PubMedGoogle Scholar
  231. Magazanik, L. G., and Vyskocil, F., 1973, Desensitization at the motor endplate, in: Drug Receptors ( H. P. Rang, ed.), MacMillan, London, pp. 105–119.Google Scholar
  232. Magazanik, L. G., and Vyskocil, F., 1975, The effect of temperature on desensitization kinetics at the post–synaptic membrane of the frog muscle fibre, J. Physiol 249: 285–300.PubMedGoogle Scholar
  233. Magleby, K. L., and Pallotta, B. S., 1981, A study of desensitization of acetylcholine receptors using nerve–released transmitter in the frog, J. Physiol 316: 225–250.PubMedGoogle Scholar
  234. Magleby, K. L., and Stevens, C. F., 1972a, The effect of voltage on the time course of end–plate currents, J. Physiol 223: 151–171.PubMedGoogle Scholar
  235. Magleby, K. L., and Stevens, C. F., 1972b, A quantitative description of end–plate currents, J. Physiol 223: 173–197.PubMedGoogle Scholar
  236. Martinez–Carrion, M., Sator, V., and Raftery, M. A., 1975, The molecular weight of an acetylcholine receptor isolated from Torpedo californica, Biophys. Res. Commun. 65: 129–137.Google Scholar
  237. McNamee, M. G., and Ochoa, E. L. M., 1982, Reconstitution of acetylcholine receptor function in model membranes, Neuroscience 7: 2305–2319.PubMedGoogle Scholar
  238. McNamee, M. G., Ellena, J. F., and Dalziel, A. W., 1982, Lipid–protein interactions in membranes containing the acetylcholine receptor, Biophys. J 37: 103–104.PubMedGoogle Scholar
  239. Mebs, D., Narita, K., Iwanaga, S., Samejima, Y., and Lee, C. Y., 1971, Amino acid sequence of a–bungarotoxin from the venom of Bungarus multicinctus. Biochem. Biophys. Res. Commun. 44: 711–716.Google Scholar
  240. Mellinger, J., Belbenoit, P., Ravaille, M., and Szabo, T., 1978, Electric organ development in Torpedo marmorata chondrichthyes, Deg. Biol 67: 167–188.Google Scholar
  241. Mendez, B., Valenzuela, P., Martial, J. A., and Baxter, J. D., 1980, Cell free synthesis of acetylcholine receptor polypeptides, Science 209: 695–697.PubMedGoogle Scholar
  242. Merlie, J. P., and Sebbane, R., 1981, Acetylcholine receptor subunits transit a precursor pool before acquiring abungarotoxin binding activity, J. Biol. Chem 256: 3605–3608.PubMedGoogle Scholar
  243. Merlie, J. P., Changeux, J.–P., and Gros, F., 1976, Acetylcholine receptor degradation measured by pulse chase labeling, Nature 264: 74–76.PubMedGoogle Scholar
  244. Merlie, J. P., Changeux, J.–P., and Gros, F., 1978, Skeletal muscle acetylcholine receptor purification, characterization and turnover in muscle cell cultures, J. Biol. Chem 253: 2882–2891.PubMedGoogle Scholar
  245. Merlie, J. P., Heineman, S., Einarson, B., and Lindstrom, J. M., 1979a, Degradation of acetylcholine receptor in diaphragms of rats with experimental autoimmune myasthenia gravis, J. Biol. Chem 254: 6328–6332.PubMedGoogle Scholar
  246. Merlie, J. P., Heinemann, S., and Lindstrom, J. M., 1979b, Acetylcholine receptor degradation in adult rat diaphragms in organ culture and the effect of anti–acetylcholine receptor antibodies, J. Biol. Chem 254: 6302–6327.Google Scholar
  247. Merlie, J. P., Hofler, J. G., and Sebbane, R., 1981, Acetylcholine receptor synthesis from membrane polysomes, J. Biol. Chem 256: 6995–6999.PubMedGoogle Scholar
  248. Merlie, J. P., Sebbane, R., Tzartos, S., and Lindstrom, J., 1982, Inhibition of glycosylation with tunicamycin blocks assembly of newly synthesized acetylcholine receptor subunits in muscle cells, J. Biol. Chem 257: 2694–2701.PubMedGoogle Scholar
  249. Meyer, D. I., Krause, E., and Dobberstein, B., 1982, Secretory protein translocation across membranes-the role of the “docking protein ”Nature 297: 647–650.PubMedGoogle Scholar
  250. Michaelson, D. M., and Raftery, M. A., 1974, Purified acetylcholine receptor: Its reconstitution to a chemically excitable membrane, Proc. Nat!. Acad. Sci. USA 71: 4768–4772.PubMedGoogle Scholar
  251. Michler, A., and Sakmann, B., 1980, Receptor stability and channel conversion in the subsynaptic membrane of the developing mammalian neuromuscular junction, Dev. Biol. 80: 1–17.Google Scholar
  252. Miller, C., Arvan, P., Telford, J. N., and Racker, E., 1976, Calcium–induced fusion of proteoliposomes: Dependence on transmembrane osmotic gradient, J. Membr. Biol 30: 271–282.PubMedGoogle Scholar
  253. Miller, D. L., Moore, H.-P. H., Hartig, P. R., and Raftery, M. A., 1978, Fast cation flux from Torpedo californica membrane preparations: Implications for a functional role for acetylcholine receptor dimers, Biochem. Biophys. Res. Commun 85: 632–640.PubMedGoogle Scholar
  254. Mishina, M., Kurosaki, T., Tobimatsu, T., Morimoto, Y., Noda, M., Yamamoto, T., Terao, M., Lindstrom, J., Takahashi, T., Kuno, M. and Numa, S., 1984, Expression of functional acetylcholine receptor from cloned cDNAs, Nature, 307: 604–608.PubMedGoogle Scholar
  255. Mochly–Rosen, C., and Fuchs, S., 1981, Monoclonal anti–acetylcholine receptor antibodies directed against the cholinergic binding site, Biochemistry 20: 5920–5924.Google Scholar
  256. Momoi, M. Y., and Lennon, V. A., 1982, Purification and biochemical characterization of nicotinic acetylcholine receptor of human muscle, J. Biol. Chem 257: 12757–12764.PubMedGoogle Scholar
  257. Montai, M., 1974, Formation of bimolecular membranes from lipid monolayers, Meth. Enzymol. 32:545–556. Montal, M., and Mueller, P., 1972, Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties, Proc. Natl. Acad. Sci. USA 69: 3561–3566.Google Scholar
  258. Montal, M., Darszon, A., and Schindler, H., 1981, Functional reassembly of membrane proteins in planar lipid bilayers, Quart. Rev. Biophys 14: 1–79.Google Scholar
  259. Montal, M., Labarca, P., Fredkin, D. R., Suarez-Isla, B. A. and Lindstrom, J.. 1984, Channel properties of the purified acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayer membranes, Biophys. J 45: 165–174.PubMedGoogle Scholar
  260. Moore, H.-P. H., and Raftery, M. A., 1979, Ligand-induced interconversion of affinity states in membrane–bound acetylcholine receptor from Torpedo californica. Effects of sulfhydryl and disulfide reagents, Biochemistry 18: 1907–1911.PubMedGoogle Scholar
  261. Moore, H.–P. H., and Raftery, M. A., 1980, Direct spectroscopic studies of cation translocation by Torpedo acetylcholine receptor on a time scale of physiological relevance, Proc. Natl. Acad. Sci. USA 77: 4509–4513.PubMedGoogle Scholar
  262. Moore, H.–P., Hartig, P. R., and Raftery, M. A., 1979, Correlation of polypeptide composition with functional events in acetylcholine receptor–enriched membranes from Torpedo californica, Proc. Natl. Acad. Sci. USA 76: 6265–6269.Google Scholar
  263. Morris, C.,E., Jackson, M. B., Lecar, H., Wong, B. S., and Christian, C. N., 1982, Activation of individual acetylcholine channels by curare in embryonic rat muscle, Biophys. J 37: 19a.Google Scholar
  264. Nachmansohn, D., 1953, Metabolism and function of the nerve cell, Harvey Lect. 49: 57–99.PubMedGoogle Scholar
  265. Nathanson, N. M., and Hall, Z. W., 1979, Subunit structure and peptide mapping of junctional and extrajunctional acetylcholine receptors from rat muscle, Biochemistry 18: 3392–3401.PubMedGoogle Scholar
  266. Nathanson, N. M., and Hall, Z. W., 1980, In situ labeling of Torpedo and rat muscle acetylcholine receptor by a,photoaffinity derivative of a–bungarotoxin, J. Biol. Chem 255: 1698–1703.Google Scholar
  267. Neher, E., and Sakmann, B., 1976, Single channel currents recorded from membrane of denervated frog muscle fibers, Nature 260: 799–802.PubMedGoogle Scholar
  268. Neher, E., and Steinbach, J. H., 1978, Local anesthetics transiently block currents through single acetylcholine receptor channels, J. Physiol 277: 153–176.PubMedGoogle Scholar
  269. Nelson, N., Anholt, R., Lindstrom, J., and Montal, M., 1980, Reconstitution of purified acetylcholine receptors with functional ion channels in planar lipid bilayers, Proc. Natl. Acad. Sci. USA 77: 3057–3061.PubMedGoogle Scholar
  270. Neubig, R. R., and Cohen, J. B., 1979, Equilibrium binding of 3H–tubocurarine and 3H–acetylcholine by Torpedo postsynaptic membranes: Stoichiometry and ligand interactions, Biochemistry 18: 5464–5475.PubMedGoogle Scholar
  271. Neubig, R. R., and Cohen, J. B., 1980, Permeability control by cholinergic receptors in Torpedo postsynaptic membranes: Agonist dose—response relations measured at second and millisecond times, Biochemistry 19: 2770–2779.PubMedGoogle Scholar
  272. Neubig, R. R., Krodel, E. K., Boyd, N. D., and Cohen, J. B., 1979, Acetylcholine and local anesthetic binding to Torpedo nicotinic postsynaptic membranes after removal of nonreceptor peptides, Proc. Natl. Acad. Sci. USA 76: 690–694.PubMedGoogle Scholar
  273. Neubig, R. R., Boyd, N. D., and Cohen, J. B., 1982, Conformations of Torpedo acetylcholine receptor associated with ion transport and desensitization, Biochemistry 21: 3460–3467.PubMedGoogle Scholar
  274. Neugebauer, D.–Ch., and Zingsheim, H. P., 1982, Structural changes in alkaline–treated postsynaptic membranes from Torpedo marmorata are not due to lipid hydrolysis, Biochim. Biophys. Acta 684: 272–276.PubMedGoogle Scholar
  275. Nghiem, H. O., Cartaud, J., Dubreuil, C., Kordeli, C., Buttin, G., and Changeux, J. P., 1983, Production and characterization of a monoclonal antibody directed against the 43,000 dalton 1,1 polypeptide from Torpedo marmorata electric organ, Proc. Natl. Acad. Sci. USA 80: 6403–6407.PubMedGoogle Scholar
  276. Nickel, E., and Potter, L. T., 1970, Synaptic vesicles in freeze–etched electric tissue of Torpedo, Brain Res. 23: 95–100.Google Scholar
  277. Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Furotani, Y., Hirose, T., Asai, M., Inayama, S., Miyata, T., and Numa, S., 1982, Primary structure of a–subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence, Nature 299: 793–797.PubMedGoogle Scholar
  278. Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Kikyotani, S., Hirose, T., Asai, M., Takashima, H., Inayama, S., Miyata, T., and Numa, S., 1983a, Primary structures of 3– and 8–subunit precursors of Torpedo californica acetylcholine receptor deduced from cDNA sequences, Nature 301: 251–255.Google Scholar
  279. Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Kikyotani, S., Furutani, Y., Hirose, T., Takashima, H., Inayama, S., Miyata, T., and Numa, S., 1983b, Structural homology of Torpedo californica acetylcholine receptor subunits, Nature 302: 528–532.PubMedGoogle Scholar
  280. Noda, M., Furutani, Y., Takahashi, H., Toyosato, M., Tanabe, T., Schimizu, S., Kikyotani, S., Kayano, T., Hirose, T., Inayama, S., and Numa, S., 1983c, Cloning and sequence analysis of calf cDNA and human genomic DNA encoding a–subunit precursor of muscle acetylcholine receptor, Nature 305: 818–823.PubMedGoogle Scholar
  281. O’Brien, D. F., Costa, L. F., and Ott, R. A., 1977, Photochemical functionality of rhodopsin–phospholipid recombinant membranes, Biochemistry 16: 1295–1303.PubMedGoogle Scholar
  282. Ochoa, E. L. M., Dalziel, A. W., and McNamee, M. G., 1983, Reconstitution of acetylcholine receptor function in lipid vesicles of defined compositions, Biochim. Biophys. Acta, 727: 151–162.PubMedGoogle Scholar
  283. Ogden, D. C., Siegelbaum, S. A., and Colquhoun, D., 1981, Block of acetylcholine–activated ion channels by an uncharged local anaesthetic, Nature 289: 596–598.PubMedGoogle Scholar
  284. Oswald, R. E., and Changeux, J.–P., 198la, Selective labeling of the 8–subunit of the acetylcholine receptor by a covalent local anesthetic, Biochemistry 20: 7166–7174.Google Scholar
  285. Oswald, R., and Changeux, J.–P., 1981b, Ultraviolet light–induced labeling by noncompetitive blockers of the acetylcholine receptor from Torpedo marmorata, Proc. Natl. Acad. Sci. USA 78: 3925–3929.Google Scholar
  286. Oswald, R. E., and Changeux, J. P., 1982, Crosslinking of abungarotoxin to the acetylcholine receptor from Torpedo marmorata by ultraviolet light irradiation, FEBS Lett. 139: 225–229.PubMedGoogle Scholar
  287. Oswald, R., Sobel, A., Waksman, G., Roques, B., and Changeux, J.–P., 1980, Selective labeling by [3H]trimethisoquin azide of polypeptide chains present in acetylcholine receptor–rich membranes from Torpedo marmorata, FEBS Lett. 111: 29–34.Google Scholar
  288. Paraschos, A., Gonzales–Ros, J., and Martinez–Carrion, M., 1982, Acetylcholine receptor from Torpedo: Preferential solubilization and efficient reintegration into lipid vesicles, Biochim. Biophys. Acta 691: 249–260.Google Scholar
  289. Parisi, M., Rivas, E., and De Robertis, E., 1971, Conductance changes produced by acetylcholine in lipidic membranes containing a proteolipid from Electrophorus, Science 172: 56–57.Google Scholar
  290. Peper, K., Dryer, F., and Mueller, K.–D., 1975, Analysis of cooperativity of drug–receptor interaction by quantitative iontophoresis at frog motor end plates, Cold Spring Harbor Symp. Quant. Biol 40: 187–192.Google Scholar
  291. Perrelet, A., Garcia–Segura, L.–M., Singh, A., and Orci, L., 1982, Distribution of cytochemically detectable cholesterol in the electric organ of Torpedo marmorata, Proc. Natl. Acad. Sci. USA 79: 2598–2602.Google Scholar
  292. Popot, J.-L., 1982, Functional studies of purified integral membrane proteins reintegrated into lipid vesicles: The case of the acetylcholine receptor, in: Méthodologie des Liposomes/Liposome Methodology (L. D. Leserman and J. Barbet,), INSERM Symposia Series 107, pp. 93–124 and 147–154.Google Scholar
  293. Popot, J.–L., Demel, R. A., Sobel, A., Van Deenen, L. L. M., and Changeux, J.–P., 1978, Interaction of the acetylcholine (nicotinic) receptor protein from Torpedo marmorata electric organ with monolayers of pure lipids, J. Biochem 85: 27–42.Google Scholar
  294. Popot, J.–L., Cartaud, J., and Changeux, J.–P., 1981, Reconstitution of a functional acetylcholine receptor: Incorporation into artificial lipid vesicles and pharmacology of the agonist–controlled permeability changes, Eur. J. Biochem 118: 203–214.PubMedGoogle Scholar
  295. Porter, C. W., and Barnard, E. A., 1975, Distribution and density of cholinergic receptors at the motor endplates of a denervated mouse muscle, Exp. Neurol 48: 542–556.PubMedGoogle Scholar
  296. Potter, L. T., and Smith, D. S., 1977, Postsynaptic membranes in the electric tissue of Narcine, Tissue Cell 9: 585–644.PubMedGoogle Scholar
  297. Prives, J., and Bar–Sagi, D., 1982, Effect of tunicamycin, an inhibitor of protein glycosylation, on the functional properties of acetylcholine receptors in cultured muscle cells, J. Cell Biol 95: 416a.Google Scholar
  298. Prives, J. M., and Olden, K., 1980, Carbohydrate requirement for expression and stability of acetylcholine receptor on the surface of embryonic muscle cells in culture, Proc. Natl. Acad. Sci. USA 77: 5263–5267.PubMedGoogle Scholar
  299. Pumplin, D. W., and Fambrough, D. M., 1982, Turnover of acetylcholine receptors in skeletal muscle, Annu. Rev. Physiol 44: 319–335.PubMedGoogle Scholar
  300. Quast, U., Schimerlik, M., Lee, T., Witzemann, V., Blanchard, S., and Raftery, M. A., 1978, Ligand–induced conformation changes in Torpedo californica membrane–bound acetylcholine receptor, Biochemistry 17: 2405–2414.PubMedGoogle Scholar
  301. Quast, U., Schimerlik, M. I., and Raftery, M. A., 1979, Ligand–induced changes in membrane–bound acetylcholine receptor observed by ethidium fluorescence. 2. Stopped–flow studies with agonists and antagonists, Biochemistry 18: 1891–1901.PubMedGoogle Scholar
  302. Raftery, M. A., Hunkapiller, M. W., Strader, C. D., and Hood, L. E., 1980, Acetylcholine receptor: Complex of homologous subunits, Science 208: 1454–1457.PubMedGoogle Scholar
  303. Rang, H. P., and Ritter, J. M., 1970, On the mechanism of desensitization at cholinergic receptors, Mol. Pharmacol 6: 357.PubMedGoogle Scholar
  304. Rang, H. P., and Ritter, J. M., 1971, The effect of disulfide bond reduction on the properties of cholinergic receptors in chick muscle, Mol. Pharmacol 7: 620–631.PubMedGoogle Scholar
  305. Ravdin, P. M., and Berg, D. K., 1979, Inhibition of neuronal acetylcholine sensitivity by a–toxins from Bungarus multicinctus venom, Proc. Natl. Acad. Sci. USA 76: 2072–2076.PubMedGoogle Scholar
  306. Reiness, C. G. and Hall, Z. W., 1977, Electrical stimulation of denervated muscles reduces incorporation of methionine into the ACh receptor, Nature 268: 655–657.PubMedGoogle Scholar
  307. Reiness, C. G., and Weinberg, C. B., 1981, Metabolic stabilization of acetylcholine receptors at newly formed neuromuscular junctions in rat, Dev. Biol 84: 247–254.PubMedGoogle Scholar
  308. Reiness, C. G., Weinberg, C. B., and Hall, Z. W., 1978, Antibody to acetylcholine receptor increases the degradation of junctional and extrajunctional receptors in adult muscles, Nature 274: 68–70.PubMedGoogle Scholar
  309. Reynolds, J. A., and Karlin, A., 1978, Molecular weight in detergent solution of acetylcholine receptor from Torpedo californica, Biochemistry 17: 2035–2038.Google Scholar
  310. Ritchie, A. K., and Fambrough, D. M., 1975, Ionic properties of the acetylcholine receptor in cultured rat myotubes, J. Gen. Physiol 65: 751–767.PubMedGoogle Scholar
  311. Ross, M. J., Klymkowsky, M. W., Agard, D. A., and Stroud, R. M., 1977, Structural studies of a membrane–bound acetylcholine receptor from Torpedo californica, J. Mol. Biol. 116: 635–659.Google Scholar
  312. Rotundo, R. L., and Fambrough, D. M., 1982, Synthesis, transport and fate of acetylcholinesterase and acetylcholine receptors in cultured muscle, in: Membranes in Growth and Development, Alan R. Liss, New York, pp. 259–286.Google Scholar
  313. Ruechel, R., Watters, D., and Maelicke, A., 1981, Molecular forms and hydrodynamic properties of acetylcholine receptor from electric tissue, Eur. J. Biochem 119: 215–223.Google Scholar
  314. Ruff, R. L., 1977, A quantitative analysis of local anaesthetic alteration of miniature end–plate currents and end-plate current fluctuations, J. Physiol 264: 89–124.PubMedGoogle Scholar
  315. Ruff, R. L., 1982, The kinetics of local anesthetic blockade of end–plate channels, Biophys. J 37: 625–631.PubMedGoogle Scholar
  316. Sahashi, K., Engel, A. G., Lindstrom, J. M., Lambert, E. M., and Lennon, V. A., 1978, Ultrastructural localization of immune complexes (IgG and C3) at the endplate in experimental autoimmune myasthenia gravis, J. Neuropathol. Exp. Neurol 37: 212–223.Google Scholar
  317. Saitoh, T., and Changeux, J.–P., 1980, Phosphorylation in vitro of membrane fragments from Torpedo marmorata electric organ: Effect on membrane solubilization by detergents, Eur. J. Biochem 105: 51–62.PubMedGoogle Scholar
  318. Saitoh, T., and Changeux, J.–P., 1981, Change in state of phosphorylation of acetylcholine receptor during maturation of the electromotor synapse in Torpedo marmorata electric organ, Proc. Natl. Acad. Sci. USA 78: 4430–4434.PubMedGoogle Scholar
  319. Saitoh, T., Wennogle, L. P., and Changeux, J. P., 1979, Factors regulating the susceptibility of the acetylcholine receptor protein to heat inactivation, FEBS Lett. 108:489–494.Google Scholar
  320. Saitoh, T., Oswald, R., Wennogle, L. P., and Changeux, J.–P., 1980, Conditions for the selective labeling of the 66,000 dalton chain of the acetylcholine receptor by the covalent non–competitive blocker 5azido–[3H]trimethisoquin, FEBS Lett. 116: 30–36.PubMedGoogle Scholar
  321. Sakmann, B., and Brenner, H. R., 1978, Change in synaptic channel gating during neuromuscular development, Nature 276: 401–402.PubMedGoogle Scholar
  322. Sakmann, B., Patlak, J., and Neher, E., 1980, Single acetylcholine–activated channels show burst–kinetics in presence of desensitizing concentrations of agonist, Nature 286: 71–73.PubMedGoogle Scholar
  323. Sanes, J. R., Marshall, L. M., and McMahan, U. J., 1978, Reinnervation of muscle fiber basal lamina after removal of myofibers: Differentiation of regenerating axons at original synaptic sites, J. Cell Biol 78: 38–165.Google Scholar
  324. Sargent, P. B., Hedges, B. E., Tsavaler, L., Clemmons, L., Tzartos, S., and Lindstrom, J., 1984, The structure and transmembrane nature of the acetylcholine receptor in amphibian skeletal muscle as revealed by crossreacting monoclonal antibodies, J. Cell Biol (in press.)Google Scholar
  325. Schiebler, W., and Hucho, F., 1978, Membranes rich in acetylcholine receptor: Characterization and reconstitution to excitable membranes from exogenous lipids, Eur. J. Biochem 85: 55–63.PubMedGoogle Scholar
  326. Schiebler, W., Bandini, G., and Hucho, F., 1980, Quaternary structure and reconstitution of acetylcholine receptor from Torpedo californica, Neurochem. Int. 2: 281–290.Google Scholar
  327. Schindler, H., 1980, Formation of planar bilayers from artificial or native membrane vesicles, FEBS Lett. 122: 77–79.PubMedGoogle Scholar
  328. Schindler, H., and Quast, U., 1980, Functional acetylcholine receptor from Torpedo marmorata in planar membranes, Proc. Natl. Acad. Sci. USA 77: 3052–3056.PubMedGoogle Scholar
  329. Schlieper, P., and De Robertis, E., 1977, Lipid bilayers and liposomes in reconstitution experiments with cholinergic proteolipid from Torpedo electroplax, Biochem. Biophys. Res. Commun 75: 886–894PubMedGoogle Scholar
  330. Schmidt, J., and Raftery, M. A., 1973, A simple assay for the study of solubilized acetylcholine receptors, Anal. Biochem 52: 349–354.Google Scholar
  331. Scubon–Mulieri, B., and Parsons, R. L., 1977, Desensitization and recovery at the frog neuromuscular junction, J. Gen. Physiol 69: 431–447.Google Scholar
  332. Scubon–Mulieri, B., and Parsons, R. L., 1978, Desensitization onset and recovery at the potassium depolarized frog neuromuscular junction are voltage sensitive, J. Gen. Physiol 71: 285–299Google Scholar
  333. Sealock, R., 1982a, Cytoplasmic surface structure in postsynaptic membranes from electric tissue visualized by tannic–acid–mediated negative contrasting, J. Cell Biol 92: 514–522.Google Scholar
  334. Sealock, R., 1982b, Visualization at the mouse neuromuscular junction of a submembrane structure in common with Torpedo postsynaptic membranes, J. Neurosci 2: 918–923.PubMedGoogle Scholar
  335. Sebbane, R., Clokey, G., Merlie, J. P., Tzartos, S., and Lindstrom, J., 1983, Characterization of the mRNA for mouse muscle acetylcholine receptor a–subunit by quantitative translation in vitro, J. Biol. Chem. 258: 3294–3303.Google Scholar
  336. Sheridan, R. E., and Lester, H. A., 1975, Relaxation measurements on the acetylcholine receptor, Proc. Natl. Acad. Sci. USA 72: 3496–3500.PubMedGoogle Scholar
  337. Sheridan, R. E., and Lester, H. A., 1977, Rates and equilibria at the acetylcholine receptor of Electrophorus electroplaques, J. Gen. Physiol 70: 187–219.PubMedGoogle Scholar
  338. Shorr, R. G., Dolly, J. O., and Barnard, E. A., 1978, Composition of acetylcholine receptor protein from skeletal muscle, Nature 274: 283–284.PubMedGoogle Scholar
  339. Shorr, R. G., Lyddiatt, A., Lo, M. M. S., Dolly, J. O., and Barnard, E. A., 1981, Acetylcholine receptor from mammalian skeletal muscle: Oligomeric forms and their subunit structures, Eur. J. Biochem 116: 143–153.PubMedGoogle Scholar
  340. Sine, S., and Taylor, P., 1979, Functional consequences of agonist–mediated state transitions in the cholinergic receptor, J. Biol. Chem 254: 3315–3325.PubMedGoogle Scholar
  341. Sine, S. M., and Taylor, P., 1980, The relationship between agonist occupation and the permeability response of the cholinergic receptor revealed by bound cobra a–toxin, J. Biol. Chem 255: 10144–10156.PubMedGoogle Scholar
  342. Sine, S. M., and Taylor, P., 1981, Relationship between reversible antagonist occupancy and the functional capacity of the acetylcholine receptor, J. Biol. Chem 256: 6692–6699.PubMedGoogle Scholar
  343. Sine, S. M., and Taylor, P., 1982, Local anesthetics and histrionicotoxin are allosteric inhibitors of the acetylcholine receptor, J. Biol. Chem 257: 8106–8114.PubMedGoogle Scholar
  344. Sokolovsky, M., and Bartfai, T., 1981, Biochemical studies on muscarinic receptors, Trends Biochem. Sci 6: 303–305.Google Scholar
  345. Smilowitz, H., Hadjian, R. A., Dwyer, J., and Feinstein, M. B., 1981, Regulation of acetylcholine receptor phosphorylation by calcium and calmodulin, Proc. Natl. Acad. Sci. USA 78: 4708–4712.PubMedGoogle Scholar
  346. Sobel, A., Weber, M., and Changeux, J.–P., 1977, Large–scale purification of the acetylcholine–receptor protein in its membrane–bound and detergent–extracted forms from Torpedo marmorata electric organ, Eur. J. Biochem 80: 215–224.PubMedGoogle Scholar
  347. Sobel, A., Heidmann, T., Hofler, J., and Changeux, J.–P., 1978, Distinct protein components from Torpedo marmorata membranes carry the acetylcholine receptor site and the binding site for local anesthetics and histrionicotoxin, Proc. Natl. Acad. Sci. USA 75: 510–514.PubMedGoogle Scholar
  348. Sobel, A., Heidmann, T., Cartaud, J., and Changeux, J.–P., 1980, Reconstitution of a functional acetylcholine receptor, Eur. J. Biochem 110: 13–33.PubMedGoogle Scholar
  349. Stanley, E. F., and Drachman, D. B., 1978, Effect of myasthenic immunoglobulin on acetylcholine receptors of intact mammalian neuromuscular junctions, Science 200: 1285–1287.PubMedGoogle Scholar
  350. Steinbach, A. B., 1968, Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end plate potential, J. Gen. Physiol 52: 144–161.PubMedGoogle Scholar
  351. Steinbach, J. H., 1981, Developmental changes in acetylcholine receptor aggregates at rat skeletal neuromuscular junctions, Dey. Biol 84: 267–276.Google Scholar
  352. Steinbach, J. H., Merlie, J., Heinemann, S., and Bloch, R., 1979, Degradation of junctional and extra–junctional acetylcholine receptors by developing rat skeletal muscle, Proc. Natl. Acad. Sci. USA 76: 3547–3551.PubMedGoogle Scholar
  353. Stephenson, F. A., Harrison, R., and Lunt, G. G., 1981, The isolation and characterization of the nicotinic acetylcholine receptor from human skeletal muscle, Eur. J. Biochem 115: 91–97.PubMedGoogle Scholar
  354. St. John, P. A., Froehner, S. C., Goodenough, D. A., and Cohen, J. B., 1982, Nicotinic postsynaptic membranes from Torpedo: Sidedness, permeability to macromolecules, and topography of major polypeptides, J. Cell Biol 92: 333–342.Google Scholar
  355. Strader, C. D., and Raftery, M. A., 1980, Topographic studies of Torpedo acetylcholine receptor subunits as a transmembrane complex, Proc. Natl. Acad. Sci. USA 77: 5807–5811.PubMedGoogle Scholar
  356. Strader, C. B. D., Revel, J.–P., and Raftery, M. A., 1979, Demonstration of the transmembrane nature of the acetylcholine receptor by labeling with anti–receptor antibodies, J. Cell Biol 83: 499–510Google Scholar
  357. Strader, C. D., Lazarides, E., and Raftery, M. A., 1980, The characterization of actin associated withpostsynaptic membranes from Torpedo californica, Biochem. Biophys. Res. Commun. 92: 365–373Google Scholar
  358. Suarez–Isla, B. A., and Hucho, F., 1977, Acetylcholine receptor: –SH group reactivity as indicator of conformational changes and functional states, FEBS Lett. 75: 65–69.Google Scholar
  359. Suarez-Isla, B. A., Wan, K., Lindstrom, J., and Montai, M., 1983, Single–channel recordings from purified acetylcholine receptors reconstituted in bilayers formed at the tip of patch pipets, Biochemistry 22, 2319–2323.PubMedGoogle Scholar
  360. Sugiyama, H., and Changeux, J.–P., 1975, Interconversion between different states of affinity for acetylcholine of the cholinergic receptor protein from Torpedo marmorata, Eur. J. Biochem. 55: 505–515.Google Scholar
  361. Sumikawa, K., Houghton, M., Emtage, J. S., Richards, B. M., and Barnard, E. A., 1981, Active multi–subunit ACh receptor assembly by translation of heterologous mRNA in Xenopus oocytes, Nature 292: 862–864.PubMedGoogle Scholar
  362. Sumikawa, K., Barnard, E. A., and Dolly, J. O., 1982a, Similarity of acetylcholine receptors of denervated, innervated and embryonic chicken muscles, Eur. J. Biochem 126: 473–479.PubMedGoogle Scholar
  363. Sumikawa, K., Houghton, M., Smith, J. C., Bell, L., Richards, B. H., and Barnard, E. A., 1982b, The molecular cloning and characterization of cDNA coding for the a–subunit of the acetylcholine receptor, Nucleic Acid Res. 10: 5809–5822.PubMedGoogle Scholar
  364. Takeuchi, N., 1963, Some properties of conductance changes at the end–plate membrane during the action of acetylcholine, J. Physiol 167: 128–140.PubMedGoogle Scholar
  365. Takeuchi, A., and Takeuchi, N., 1960, On the permeability of end–plate membrane during the action of transmitter, J. Physiol 154: 52–67.PubMedGoogle Scholar
  366. Tank, D. W., Huganir, R. L., Greengard, P., and Webb, W. W., 1983, Patch–recorded single channel currents of the purified and reconstituted Torpedo acetylcholine receptor, Proc. Natl. Acad. Sci. USA 80: 5129–5133.PubMedGoogle Scholar
  367. Tarrab–Hazdai, R., Geiger, B., Fuchs, S., and Amsterdam, A., 1978, Localization of acetylcholine receptor in excitable membrane from the electric organ of Torpedo: Evidence for exposure of receptor antigenic sites on both sides of the membrane, Proc. Natl. Acad. Sci. USA 75: 2497–2501.Google Scholar
  368. Tauc, L., 1982, Nonvesicular release of neurotransmitter, Physiol. Rev 62: 857–891.PubMedGoogle Scholar
  369. Teichberg, V. I., Sobel, A., and Changeux, J.–P., 1977, In vitro phosphorylation of the acetylcholine receptor, Nature 267: 540–542.Google Scholar
  370. Trautmann, A., 1982, Curare can open and block ionic channels associated with cholinergic receptors, Nature 298: 272–275.PubMedGoogle Scholar
  371. Trautmann, A., and Feltz, A., 1980, Open time of channels activated by binding of two distinct agonists, Nature 286: 291–293.PubMedGoogle Scholar
  372. Tzartos, S. J., and Changeux, J.-P., 1982, Lipid–dependent recovery of high affinity binding of a–bungarotoxin to the purified a–subunit from Torpedo acetylcholine receptors, Abstracts, Society for Neuroscience, 12th Annual Meeting, Minneapolis, Minnesota, 91. 4, p. 334.Google Scholar
  373. Tzartos, S. J., and Lindstrom, J. M., 1980, Monoclonal antibodies used to probe acetylcholine receptor structure: Localization of the main immunogenic region and detection of similarities between subunits, Proc. Natl. Acad. Sci. USA 77: 755–759.Google Scholar
  374. Tzartos, S. J., Rand, D. E., Einarson, B. L., and Lindstrom, J. M., 1981, Mapping of surface structures of Electrophorus acetylcholine receptor using monoclonal antibodies, J. Biol. Chem 256: 8635–8645.PubMedGoogle Scholar
  375. Tzartos, S. J., Seybold, M. E., and Lindstrom, J. M., 1982, Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies, Proc. Nat!. Acad. Sci. USA 79: 188–192.PubMedGoogle Scholar
  376. Tzartos, S., Langeberg, L., Hochschwender, S., and Lindstrom, J., 1983, Demonstration of a main immunogenic region on acetylcholine receptors from human muscle using monoclonal antibodies to human receptor, FEBS Lett. 158: 116–118.PubMedGoogle Scholar
  377. Vandlen, R. L., Wu, W. C.-S., Eisenach, J. C., and Raftery, M. A., 1979, Studies of the composition of purified Torpedo californica acetylcholine receptor and of its subunits, Biochemistry 18: 1845–1854.PubMedGoogle Scholar
  378. Verdenhalven, Y., Bandini, G., and Hucho, F., 1982, Acetylcholine receptor–rich membranes contain an endogenous protease regulated by peripheral membrane protein, FEBS Lett. 147: 168–170.PubMedGoogle Scholar
  379. Vincent, A., 1980, Immunology of acetylcholine receptors in relation to myasthenia gravis, Physiol. Rev. 60: 726–824.Google Scholar
  380. Waksman, G., Oswald, R., Changeux, J.–P., and Roques, B. P., 1980, Synthesis and pharmacological activity on Electrophorus electricus electroplaque of photoaffinity labelling derivatives of the noncompetitive blockers di–and tri–methisoquin, FEBS Lett. 111: 23–28.PubMedGoogle Scholar
  381. Walker, J. W., Lukas, R. J., and McNamee, M. G., 1981a, Effects of thio–group modifications on the ion permeability control and ligand binding properties of Torpedo californica acetylcholine receptor, Biochemistry 20: 2191–2199.PubMedGoogle Scholar
  382. Walker, J. W., McNamee, M. G., Pasquale, E., Cash, D. J., and Hess, G. P., 198 lb, Acetylcholine receptor inactivation in Torpedo californica electroplax membrane vesicles. Detection of two processes in the millisecond and second time regions, Biochem. Biophys. Res. Commun 100: 86–90.Google Scholar
  383. Walker, J. W., Takeyasu, K., and McNamee, M. G., 1982, Activation and inactivation kinetics of Torpedo californica acetylcholine receptor in reconstituted membranes, Biochemistry 21: 5384–5389.PubMedGoogle Scholar
  384. Walkinshaw, M. D., Saenger, W., and Maelicke, A., 1980, Three–dimensional structure of the long neurotoxin from cobra venom, Proc. Natl. Acad. Sci. USA 77: 2400–2404.PubMedGoogle Scholar
  385. Walter, P., and Blobel, G., 1981a, Translocation of proteins across the endoplasmic reticulum. II. Signal recognition protein (SRP) mediates the selective binding to microsomal membranes of in vitro assembled polysomes synthesizing secretory protein, J. Cell Biol 91: 551–556.PubMedGoogle Scholar
  386. Walter, P., and Blobel, G., 198 lb, Translocation of proteins across the endoplasmic reticulum. III. Signal recognition protein (SRP) causes signal sequence–dependent and site–specific arrest of chain elongation that is released by microsomal membranes, J. Cell Biol. 91:557–561. Walter, P. Ibrahimi, I., and Blobel, G., 1981, Translocation of proteins across the endoplasmic reticulum.Google Scholar
  387. I. Signal recognition protein (SRP) binds to in vitro–assembled polysomes synthesizing secretory protein,J. Cell Biol 91:545–550.Google Scholar
  388. Weber, M., David–Pfeuty, T., and Changeux, J.–P., 1975, Regulation of binding properties of the nicotinic receptor protein by cholinergic ligands in membrane fragments from Torpedo marmorata, Proc. Natl. Acad. Sci. USA 72: 3443–3447.Google Scholar
  389. Weiland, G., and Taylor, P., 1979, Ligand specificity of state transitions in the cholinergic receptor: Behavior of agonists and antagonists, Mol. Pharmacol 15: 197–212.PubMedGoogle Scholar
  390. Weiland, G., Georgia, B., Wee, V. T., Chignell, C. F., and Taylor, P., 1976, Ligand interactions with cholinergic receptor–enriched membranes from Torpedo: Influence of agonist exposure on receptor properties, Mol. Pharmacol 12: 1091–1105.PubMedGoogle Scholar
  391. Weiland, G., Georgia, B., Lappi, S., Chignell, C. F., and Taylor, P., 1977, Kinetics of agonist–mediated transitions in state of the cholinergic receptor, J. Biol. Chem 252: 7648–7656.PubMedGoogle Scholar
  392. Weill, C. L., McNamee, M. G., and Karlin, A., 1974, Affinity–labeling of purified acetylcholine receptor from Torpedo californica, Biochem. Biophys. Res. Commun. 61: 997–1003.Google Scholar
  393. Weinberg, C. G., and Hall, Z. W., 1979, Antibodies from patients with myasthenia gravis recognize determinants unique to extrajunctional acetylcholine receptors, Proc. Natl. Acad. Sci. USA 76: 504–508.PubMedGoogle Scholar
  394. Wennogle, L. P., and Changeux, J.–P., 1980, Transmembrane orientation of proteins present in acetylcholine receptor–rich membranes from Torpedo marmorata studied by selective proteolysis, Eur. J. Biochem 106: 381–393.PubMedGoogle Scholar
  395. Wennogle, L. P., Oswald, R., Saitoh, T., and Changeux, J.–P., 1981, Dissection of the 66,000 dalton subunit of the acetylcholine receptor, Biochemistry 20: 2492–2497.PubMedGoogle Scholar
  396. Wise, D. S., Karlin, A., and Schoenborn, B. P., 1979, An analysis by low–angle neutron scattering of the structure of the acetylcholine receptor from Torpedo californica in detergent solution, Biophys. J 28: 473–496.PubMedGoogle Scholar
  397. Wise, D. S., Schoenborn, B. P., and Karlin, A., 1981a, Structure of acetylcholine receptor dimer determined by neutron scattering and electron microscopy, J. Biol. Chem 256: 4124–4126.PubMedGoogle Scholar
  398. Wise, D. S., Wall, J., and Karlin, A., 1981b, Relative locations of the 3– and 8–chains of the acetylcholine receptor determined by electron microscopy of isolated receptor trimer, J. Biol. Chem 256: 12624–12627.PubMedGoogle Scholar
  399. Witzemann, V., and Raftery, M. A., 1978, Affinity directed crosslinking of acetylcholine receptor poly– peptide components in post–synaptic membranes, Biochem. Biophys. Res. Commun 85: 1623–631.Google Scholar
  400. Witzemann, V., Muchmore, D., and Raftery, M. A., 1979, Affinity–directed cross–linking of membrane–bound acetylcholine receptor polypeptides with photolabile a–bungarotoxin derivatives, Biochemistry 18: 5511–5518.PubMedGoogle Scholar
  401. Wolosin, J. M., Lyddiatt, A., Dolly, J. O., and Barnard, E. A., 1980, Stoichiometry of the ligand–binding sites in the acetylcholine–receptor oligomer from muscle and from electric organ, Eur. J. Biochem 109: 495–505.PubMedGoogle Scholar
  402. Wu, W. C.–S., and Raftery, M. A., 1979, Carbamylcholine–induced rapid cation efflux from reconstituted membrane vesicles containing purified acetylcholine receptor, Biochem. Biophys. Res. Commun 89: 26–35.PubMedGoogle Scholar
  403. Wu, W. C.–S., and Raftery, M. A., 1981, Functional properties of acetylcholine receptor monomeric and dimeric forms in reconstituted membranes, Biochem. Biophys. Res. Commun 99: 436–444.PubMedGoogle Scholar
  404. Wu, W. C.–S., Moore, H.–P. H., and Raftery, M. A., 1981, Quantitation of cation transport by reconstituted membrane vesicles containing purified acetylcholine receptor, Proc. Natl. Acad. Sci. USA 78: 775–779.PubMedGoogle Scholar
  405. Young, A. P., Brown, F. F., Halsey, M. J., and Sigman, D. S., 1978, Volatile anesthetic facilitation of in vitro desensitization of membrane–bound acetylcholine receptor from Torpedo californica, Proc. Natl. Acad. Sci. USA 75: 4563–4567.Google Scholar
  406. Zingsheim, H. P., Neugebauer, D.–Ch., Barrantes, F. J., and Frank, J., 1980, Structural details of membrane–bound actylcholine receptor from Torpedo marmorata, Proc. Nad. Acad. Sci. USA 77: 952–956.Google Scholar
  407. Zingsheim, H. P., Barrantes, F. J., Frank, J., Haenicke, W., and Neugebauer, D.–Ch., 1982a, Direct structural localization of two toxin-recognition sites on an ACh receptor protein, Nature 299: 81–84.Google Scholar
  408. Zingsheim, H.–P., Neugebauer, D.–Ch., Frank, J., Haenicke, W., and Barrantes, F. J., 1982b, Dimeric arrangement and structure of the membrane–bound acetylcholine receptor studied by electron microscopy, Eur. Mol. Biol. Org. J. 1: 541–547.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Robert Anholt
    • 1
  • Jon Lindstrom
    • 1
  • Mauricio Montal
    • 2
  1. 1.The Salk Institute for Biological StudiesSan DiegoUSA
  2. 2.Departments of Biology and PhysicsUniversity of California, San DiegoLa JollaUSA

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