The Neuromuscular Junction

  • M. E. Kriebel
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 86)


Physiological studies on the neuromuscular junction (NMJ) are usually concerned with either postsynaptic receptor and channel mechanisms (Chap. 9) or with presynaptic characteristics of transmitter release (Chap. 1). The present chapter will discuss the quantal basis of transmitter release at the NMJ, emphasizing the multiplicity of classes of quanta observed and their pharmacological differences. Quanta are detected as miniature end-plate potentials (mEPPs) which may be divided into at least three main classes: skew-mEPPs, bell-mEPPs, and giant-mEPPs.


Botulinum Toxin Neuromuscular Junction Transmitter Release mEPP Amplitude Amplitude Histogram 
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  1. Augustine GJ, Levitan H (1983) Neurotransmitter release and nerve terminal morphology at the frog neuromuscular junction affected by the dye erythrosin B. J Physiol (Lond) 334:47–63Google Scholar
  2. Barker D, Ip MC (1966) Sprouting and degeneration of mammalian motor axons in normal and de-afferentated skeletal muscle. Proc R Soc Lond [Biol] 163:538–554CrossRefGoogle Scholar
  3. Bennett MR, Pettigrew AG (1974a) The formation of synapses in striated muscle during development. J Physiol (Lond) 241:515–545Google Scholar
  4. Bennett MR, Pettigrew AG (1974 b) The formation of synapses in reinnervated and crossreinnervated striated muscle during development. J Physiol (Lond) 241:547–573Google Scholar
  5. Bennett MR, Pettigrew AG (1975) The formation of synapses in amphibian striated muscle during development. J Physiol (Lond) 252:203–239Google Scholar
  6. Bennett MR, McLachlan EM, Taylor RS (1973) The formation of synapses in reinnervated mammalian striated muscle. J Physiol (Lond) 233:481–500Google Scholar
  7. Bennett MR, Florin T, Woog R (1974) The formation of synapses in regenerating mammalian striated muscle. J Physiol (Lond) 238:79–92Google Scholar
  8. Bevan S (1976) Sub-miniature end-plate potentials at untreated frog neuromuscular junctions. J Physiol (Lond) 258:145–155Google Scholar
  9. Bevan S, Grampp W, Miledi R (1973) Further observation on Schwann cell min.e.p.p.s. J Physiol (Lond) 232:88P–89PGoogle Scholar
  10. Bevan S, Grampp W, Miledi R (1976) Properties of spontaneous potentials at denervated motor end-plates of the frog. Proc R Soc Lond [Biol] 194:195–210CrossRefGoogle Scholar
  11. Bieser A, Wernig A, Zucker H (1984) Different quantal responses within single frog neuromuscular junctions. J Physiol (Lond) 350:401–412Google Scholar
  12. Birks R, Katz B, Miledi R (1960) Physiological and structural changes at the amphibian myoneural junction, in the course of nerve degeneration. J Physiol (Lond) 150:145–168Google Scholar
  13. Blight AR, Precht W (1982) Miniature endplate potentials related to neuronal injury. Brain Res 238:233–238PubMedCrossRefGoogle Scholar
  14. Boyd IA, Martin AR (1956) The end-plate potential in mammalian muscle. J Physiol (Lond) 132:74–91Google Scholar
  15. Brazil OV, Excell BJ (1971) Action of crotoxin and crotactin from the venom of Crotalus durissus terrificus (South American rattlesnake) on the frog neuromuscular junction. J Physiol (Lond) 212:34P–35PGoogle Scholar
  16. Carlson CG, Kriebel ME (1985) Neostigmine increases the size of subunits composing the quantum of neurotransmitter release at mouse neuromuscular junction. J Physiol (Lond) 367:489–502Google Scholar
  17. Carlson CG, Kriebel ME, Muniak CG (1982) The effect of temperature on MEPP amplitude distributions in the mouse diaphragm. Neuroscience 7:2537–2549PubMedCrossRefGoogle Scholar
  18. Colméus C, Gomez S, Molgó J, Thesleff S (1982) Discrepancies between spontaneous and evoked synaptic potentials at normal, regenerating and botulinum toxin poisoned mammalian neuromuscular junctions. Proc R Soc Lond [Biol] 215:63–74CrossRefGoogle Scholar
  19. Cull-Candy SG, Lundh H, Thesleff S (1976) Effects of botulinum toxin on neuromuscular transmission in the rat. J Physiol (Lond) 260:177–203Google Scholar
  20. D’Alonzo A, Grinnell AD (1985) Profiles of evoked release along the length of frog motor nerve terminals. J Physiol (Lond) 359:235–258Google Scholar
  21. Del Castillo J, Katz B (1954) Quantal components of the end-plate potential. J Physiol (Lond) 124:560–573Google Scholar
  22. Dennis MJ, Miledi R (1971) Lack of correspondence between the amplitudes of spontaneous potentials and unit potentials evoked by nerve impulses at regenerating neuromuscular junctions. Nature [New Biol] 232:126–128Google Scholar
  23. Dennis MJ, Miledi R (1974a) Non-transmitting neuromuscular junctions during an early stage of end-plate reinnervation. J Physiol (Lond) 239:553–570Google Scholar
  24. Dennis MJ, Miledi R (1974 b) Characteristics of transmitter release at regenerating frog neuromuscular junctions. J Physiol (Lond) 239:571–594Google Scholar
  25. Dennis MJ, Miledi R (1974 c) Electrically induced release of acetylcholine from denervated Schwann cells. J Physiol (Lond) 237:431–452Google Scholar
  26. Doherty P, Hawgood BJ, Smith ICH (1984) Changes in miniature end-plate potentials after brief nervous stimulation at the frog neuromuscular junction. J Physiol (Lond) 356:349–358Google Scholar
  27. Duchen LW, Tonge DA (1973) The effects of tetanus toxin on neuromuscular transmission and on the morphology of motor end-plates in slow and fast skeletal muscle of the mouse. J Physiol (Lond) 228:157–172Google Scholar
  28. Duering MV (1967) Über die Feinstruktur der motorischen Endplatte von höheren Wirbeltieren. Z Zellforsch 81:74–90CrossRefGoogle Scholar
  29. Durant NN, Marshall JD (1980) The effect of 3,4-diaminopyridine on acetylcholine release at the frog neuromuscular junction. Eur J Pharmacol 67:201–208PubMedCrossRefGoogle Scholar
  30. Erxleben C, Kriebel ME (1983) Characteristics of miniature and sub-miniature endplate currents at the mouse diaphragm endplate. Naunyn Schmiedebergs Arch Pharmacol [Suppl] 322: R 62Google Scholar
  31. Erxleben C, Kriebel ME (1988 a) Characteristics of spontaneous miniature and subminiature end-plate currents at the neonate and adult mouse neuromuscular junction. J Physiol (Lond) (in press)Google Scholar
  32. Erxleben C, Carlson G, Kriebel ME (1983) Studies of miniature endplate currents show that the quantum of release is composed of subunits. Soc Neurosci Abstr 9:88Google Scholar
  33. Fatt P, Katz B (1952) Spontaneous subthreshold activity at motor nerve endings. J Physiol (Lond) 117:109–128Google Scholar
  34. Gage PW, McBurney RN (1975) Effects of membrane potential, temperature and neostigmine on the conductance change caused by a quantum of acetylcholine at the toad neuromuscular junction. J Physiol (Lond) 244:385–407Google Scholar
  35. Gross CE, Kriebel ME (1973) Multimodal distribution of mepp amplitudes: the changing distribution with denervation, nerve stimulation and high frequencies of spontaneous release. J Gen Physiol 62:658–659aGoogle Scholar
  36. Harris AJ, Miledi R (1971) The effect of type D botulinum toxin on frog neuromuscular junctions. J Physiol (Lond) 217:497–515Google Scholar
  37. Hartzell HC, Kuffler SW, Yoshikami D (1975) Post-synaptic potentiation: Interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. J Physiol (Lond) 251:427–463Google Scholar
  38. Heinonen E, Jansson SE, Tolppanen EM (1982) Independent release of supranormal acetylcholine quanta at the rat neuromuscular junction. Neuroscience 7:21–24PubMedCrossRefGoogle Scholar
  39. Heuser J, Miledi R (1971) Effect of lanthanum ions on function and structure of frog neuromuscular junctions. Proc R Soc Lond [Biol] 179:247–260CrossRefGoogle Scholar
  40. Heuser JE, Reese TS (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J Cell Biol 57:315–344PubMedCrossRefGoogle Scholar
  41. Heuser JE, Reese TS, Dennis MJ, Jan Y, Jan L, Evans L (1979) Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J Cell Biol 81:275–300PubMedCrossRefGoogle Scholar
  42. Hubbard JI, Jones SF (1973) Spontaneous quantal transmitter release: A statistical analysis and some implications. J Physiol (Lond) 232:1–21Google Scholar
  43. Ito Y, Miledi R (1977) The effect of calcium ionophores on acetylcholine release from Schwann cells. Proc R Soc Lond [Biol] 196:51–58CrossRefGoogle Scholar
  44. Katz B (1962) The transmission of impulses from nerve to muscle, and the subcellular unit of synaptic action. Proc R Soc Lond [Biol] 155:455–477CrossRefGoogle Scholar
  45. Katz B (1977) Prologue. In: Cottrell GA, Usherwood PNR (eds) Synapses. Academic, New York, pp 1–5Google Scholar
  46. Katz B (1978) The release of the neuromuscular transmitter and the present state of the hypothesis. In: Porter R (ed) Studies in neurophysiology. Cambridge University Press, Cambridge, pp 1–21Google Scholar
  47. Katz B, Thesleff S (1957) On the factors which determine the amplitude of the ‘miniature end-plate potential’. J Physiol (Lond) 137:267–278Google Scholar
  48. Katz B, Miledi R (1977) Transmitter leakage from motor nerve endings. Proc R Soc Lond [Biol] 196:59–72CrossRefGoogle Scholar
  49. Katz B, Miledi R (1979) Estimates of quantal content during ‘chemical potentiation’ of transmitter release. Proc R Soc Lond [Biol] 205:369–378CrossRefGoogle Scholar
  50. Kelly SS, Robbins N (1984) Bimodal miniature and evoked end-plate potentials in adult mouse neuromuscular junctions. J Physiol (Lond) 346:353–363Google Scholar
  51. Kidokoro Y (1984) Two types of miniature endplate potentials in Xenopus nerve-muscle cultures. Neurosci Res 1:157–170PubMedCrossRefGoogle Scholar
  52. Kim YI, Lømo T, Lupa MT, Thesleff S (1984) Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin. J Physiol (Lond) 356:587–599Google Scholar
  53. Koenig J, Pécot-Dechavassine M (1971) Relations entre l’apparition des potentiels miniatures spontanés et l’ultrastructure des plaques motrices en voie de réinnervation et de néoformation chez le rat. Brain Res 27:43–57PubMedCrossRefGoogle Scholar
  54. Kriebel ME (1978) Small mode miniature endplate potentials are increased and evoked in fatigued preparations and in high Mg2+ saline. Brain Res 148:381–388PubMedCrossRefGoogle Scholar
  55. Kriebel ME, Erxleben C (1986) Sub-mepps, skew-mepps and the subunit hypothesis of quantal transmitter release at the neuromuscular junction. In: Rahamimoff R, Katz B (eds) Calcium, neuronal function and transmitter release. Nijhoff, Dordrecht, pp 299–329CrossRefGoogle Scholar
  56. Kriebel ME, Florey E (1983) Effect of lanthanum ions on the amplitude distributions of miniature endplate potentials and on synaptic vesicles in frog neuromuscular junctions. Neuroscience 9:535–547PubMedCrossRefGoogle Scholar
  57. Kriebel ME, Gross CE (1974) Multimodal distribution of frog miniature endplate potentials in adult, denervated, and tadpole leg muscle. J Gen Physiol 64:85–103PubMedCrossRefGoogle Scholar
  58. Kriebel ME, Motelica-Heino I (1987) Description of the sub-mepp distribution, determination of subunit size and number of subunits in the adult frog neuromuscular bellmepp. Neuroscience 23:757–766PubMedCrossRefGoogle Scholar
  59. Kriebel ME, Llados F, Matteson DR (1976) Spontaneous subminiature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release. J Physiol (Lond) 262:553–581Google Scholar
  60. Kriebel ME, Hanna RB, Pappas GD (1980) Spontaneous potentials and fine structure of identified frog denervated neuromuscular junction. Neuroscience 5:97–108PubMedCrossRefGoogle Scholar
  61. Kriebel ME, Llados F, Carlson CG (1980a) Effect of the Ca2+ ionophore X-537 A and a heat challenge on the distribution of mouse mepp amplitude histograms. J Physiol (Paris) 76:435–441Google Scholar
  62. Kriebel ME, Llados F, Matteson DR (1982) Histograms of the unitary evoked potentials of the mouse diaphragm show multiple peaks. J Physiol (Lond) 322:211–222Google Scholar
  63. Kriebel ME, Hanna R, Muniak C (1986) Synaptic vesicle diameters and synaptic cleft widths at the mouse diaphragm in neonates and adults. Dev Brain Res 27:19–29CrossRefGoogle Scholar
  64. Kuffler SW, Yoshikami D (1975) The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. J Physiol (Lond) 251:465–482Google Scholar
  65. Kullberg RW, Lentz TL, Cohen MW (1977) Development of the myotomal neuromuscular junction in Xenopus laevis an electrophysiological and fine-structural study. Dev Biol 60:101–129PubMedCrossRefGoogle Scholar
  66. Land BR, Salpeter EE, Salpeter MM (1980) Acetylcholine receptor site density affects the rising phase of miniature endplate currents. Proc Natl Acad Sci USA 77:3736–3740PubMedCrossRefGoogle Scholar
  67. Liley AW (1956 a) An investigation of spontaneous activity at the neuromuscular junction of the rat. J Physiol (Lond) 132:650–666Google Scholar
  68. Liley AW (1956b) The quantal components of the mammalian end-plate potential. J Physiol (Lond) 133:571–587Google Scholar
  69. Liley AW (1957) Spontaneous release of transmitter substance in multiquantal units. J Physiol (Lond) 136:595–605Google Scholar
  70. Llados F, Kriebel ME, Matteson DR (1980) β-Bungarotoxin preferentially blocks one class of miniature endplate potentials. Brain Res 192:598–602PubMedCrossRefGoogle Scholar
  71. Longenecker HE, Hurlbut WP, Mauro A, Clark AW (1970) Effects of a black widow spider venom on the frog neuromuscular junction: effects on endplate potential, miniature endplate potential and nerve terminal spike. Nature 225:701–703PubMedCrossRefGoogle Scholar
  72. MacDermot J, Westgaard RH, Thompson EJ (1978) Separation of two discrete proteins with different synaptic actions. Biochem J 175:271–279PubMedGoogle Scholar
  73. Magleby KL, Miller DC (1981) Is the quantum of transmitter release composed of subunits? A critical analysis of the mouse and frog. J Physiol (Lond) 311:267–287Google Scholar
  74. Magleby KL, Weinstock MM (1980) Nickel and calcium ions modify the characteristics of the acetylcholine receptor-channel complex at the frog neuromuscular junction. J Physiol (Lond) 299:203–218Google Scholar
  75. Martin AR (1966) Quantal nature of synaptic transmission. Physiol Rev 46:51–66Google Scholar
  76. Martin AR, Pilar G (1964) Quantal components of the synaptic potential in the ciliary ganglion of the chick. J Physiol (Lond) 175:1–16Google Scholar
  77. Matteson DR, Kriebel ME, Llados F (1981) A statistical model indicates that miniature end-plate potentials and unitary evoked end-plate potentials are composed of subunits. J Theor Biol 90:337–363PubMedCrossRefGoogle Scholar
  78. Matthews-Bellinger JA, Salpeter MM (1983) Fine structural distribution of acetylcholine receptors at developing mouse neuromuscular junctions. J Neurosci 3:644–657PubMedGoogle Scholar
  79. McArdle JJ, Albuquerque EX (1973) A study of the reinnervation of fast and slow mammalian muscles. J Gen Physiol 61:1–23PubMedCrossRefGoogle Scholar
  80. McLarnon JG, Quastei DMJ (1983) Postsynaptic effects of magnesium and calcium at the mouse neuromuscular junction. J Neurosci 3:1626–1633PubMedGoogle Scholar
  81. Miledi R, Slater CR (1970) On the degeneration of rat neuromuscular junctions after nerve section. J Physiol (Lond) 207:507–528Google Scholar
  82. Miller DC, Weinstock MM, Magleby KL (1978) Is the quantum of transmitter release composed of subunits? Nature 274:388–390PubMedCrossRefGoogle Scholar
  83. Miyamoto MD (1975) Binomial analysis of quantal transmitter release at glycerol treated frog neurotransmitter junctions. J Physiol (Lond) 250:121–142Google Scholar
  84. Molgó J, Thesleff S (1982) 4-aminoquinoline-induced ‘giant’ miniature endplate potentials at mammalian neuromuscular junctions. Proc R Soc Lond [Biol] 214:229–247CrossRefGoogle Scholar
  85. Monolov S, Ovtscharoff W (1982) Structure and cytochemistry of the chemical synapses. Int Rev Cytol 77:243–284CrossRefGoogle Scholar
  86. Muniak CG, Kriebel ME, Carlson CG (1982) Changes in mepp and epp amplitude distributions in the mouse diaphragm during synapse formation and degeneration. Dev Brain Res 5:123–138CrossRefGoogle Scholar
  87. Nicholls JG (1956) The electrical properties of denervated skeletal muscle. J Physiol (Lond) 131:1–12Google Scholar
  88. Pécot-Dechavassine M (1976) Action of vinblastine on the spontaneous release of acetylcholine at the frog neuromuscular junction. J Physiol (Lond) 261:31–48Google Scholar
  89. Pennefather P, Quastel DMJ (1981) Relation between subsynaptic receptor blockade and response to quantal transmitter at the mouse neuromuscular junction. J Gen Physiol 78:313–344PubMedCrossRefGoogle Scholar
  90. Rose SJ, Pappas GD, Kriebel ME (1978) The fine structure of identified frog neuromuscular junctions in relation to synaptic activity. Brain Res 144:213–239PubMedCrossRefGoogle Scholar
  91. Rotshenker S, Tal M (1985) The transneuronal induction of sprouting and synapse formation in intact mouse muscles. J Physiol (Lond) 360:387–396Google Scholar
  92. Sakmann B, Brenner HR (1978) Changes in synaptic channel gating during neuromuscular development. Nature 276:401–402PubMedCrossRefGoogle Scholar
  93. Sellin LC, Thesleff S (1981) Pre- and post-synaptic actions of botulinum toxin at the rat neuromuscular junction. J Physiol (Lond) 317:487–495Google Scholar
  94. Spitzer N (1972) Miniature end-plate potentials at mammalian neuromuscular junctions poisoned by botulinum toxin. Nature [New Biol] 237:26–27CrossRefGoogle Scholar
  95. Sun Y-A, Poo M-M (1985) Non-quantal release of acetylcholine at developing neuromuscular synapse in culture. J Neurosci 5:634–642PubMedGoogle Scholar
  96. Tonge DA (1974) Physiological characteristics of re-innervation of skeletal muscle in the mouse. J Physiol (Lond) 241:141–153Google Scholar
  97. Vautrin J, Mambrini J (1981) Caractéristiques du potentiel unitaire de plaque motrice de la grenouille. J Physiol (Paris) 77:999–1010Google Scholar
  98. Vicini S, Schuetze SM (1985) Gating properties of acetylcholine receptors at developing rat endplates. J Neurosci 5:2212–2224PubMedGoogle Scholar
  99. Wernig A (1975) Estimates of statistical release parameters from crayfish and frog neuromuscular junctions. J Physiol (Lond) 244:207–221Google Scholar
  100. Wernig A, Motelica-Heino I (1978) On the presynaptic nature of the quantal subunit. Neurosci Lett 8:231–234PubMedCrossRefGoogle Scholar
  101. Wernig A, Stirner H (1977) Quantum amplitude distributions point to functional unity of the synaptic ‘active zone’. Nature 269:820–822PubMedCrossRefGoogle Scholar
  102. Whittaker VP (1984) The synaptosome. In: Lajtha A (ed) Handbook of neurochemistry, vol 7. Plenum, New York, pp 1–39Google Scholar
  103. Young SH, Poo M (1983) Spontaneous release of transmitter from growth cones of embryonic neurones. Nature 305:634–637PubMedCrossRefGoogle Scholar
  104. Zimmermann H (1982) Insights into the functional role of cholinergic vesicles. In: Klein RL, Lagercrantz H, Zimmermann H (eds) Neurotransmitter vesicles. Academic, London, pp 305–359Google Scholar
  105. Ziskind-Conhaim L, Dennis MJ (1981) Development of rat neuromuscular junctions in organ culture. Dev Biol 85:243–251PubMedCrossRefGoogle Scholar

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  • M. E. Kriebel

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