Sub-MEPPs, Skew-MEPPs and the Subunit Hypothesis of Quantal Transmitter Release at the Neuromuscular Junction

  • M. E. Kriebel
  • C. Erxleben
Part of the Topics in the Neurosciences book series (TNSC, volume 1)


sub-MEPPs, skew-MEPPs and bell-MEPPs. In 1973 we reported that there is a class of small MEPPs (sub-MEPPs) at the normal adult frog neuromuscular junction and that the normally low percentage of these small MEPPs is temporarily increased after a heat challenge or nerve stimulation (Gross and Kriebel, 1973; Kriebel and Gross, 1974; Bevan, 1976) (Fig. 1) or with focal depolarization (Cooke and Quastel, 1973). Sub-MEPPs are absent with curare (Cooke and Quastel, 1973) and potentiated by eserine similarly to the larger MEPPs that were initially described by Fatt and Katz (1952). The larger MEPPs are termed bell-MEPPs because the amplitude distribution is bell-shaped (Fig. 2). Since both sub-MEPPs and the larger MEPPs are found in the normal preparation, the term normal-MEPP or classical-MEPP is inaccurate. The sub-MEPPs form a distinct class separate from the bell-MEPPs as indicated by the discontinuity in the profile of the MEPP amplitude histogram. In the frog neuromuscular junction, the small MEPP amplitudes usually form a bell distribution and are termed sub-MEPPs or s-MEPPs. However, in the mouse neuromuscular junction, the class of small MEPPs shows an overall skew distribution with a mode near the noise level (hence termed skew-MEPPs ; term from Harris and Miledi, 1971). The skew class of MEPPs may show integral peaks providing that enough MEPPs are present in each histobar and if adequate resolving power of the histogram is used (i.e., bins between peaks; Fig. 2; Matteson et al., 1979). When the skew-class shows multiple peaks, the first peak is the sub-MEPP (s-MEPP) and its modal value is the same as that of the overall skew-class. The skew-class thus includes the sub-MEPPS (s-MEPPs). Doublet MEPPs (two beli-MEPPs, Kriebel and Stolper, 1975), are not discussed here.


Botulinum Toxin Neuromuscular Junction Central Peak MEPP Amplitude Integral Peak 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Augustine, G.J. and H. Levitan. Neurotransmitter release and nerve terminal morphology at the frog neuromuscular junction by the dye Erythrosin B. J. Physiol. 334:47–63, 1983.PubMedGoogle Scholar
  2. Bevan, S. Sub-miniature end-plate potentials at untreated frog neuromuscular junctions. J. Physiol. 258: 145–155, 1976.PubMedGoogle Scholar
  3. Birks, R., B. Katz and R. Miledi. Physiological and structural changes at the amphibian myoneural junction in the course of nerve degeneration. J. Physiol. 150: 145–168, 1960.PubMedGoogle Scholar
  4. Boyd, I.A. and A.R. Martin. The end-plate potential in mammalian muscle. J. Physiol. 132: 74–91, 1956.PubMedGoogle Scholar
  5. Carlson, C.G., M.E. Kriebel and CG. Muniak. The effect of temperature on MEPP amplitude distributions in the mouse diaphragm. Neuroscience 7: 2537–2549, 1982.PubMedCrossRefGoogle Scholar
  6. Colméus, C., S. Gomez, J. Molgó and S. Thesleff. Discrepancies between spontaneous and evoked synaptic potentials at normal, regenerating and botulinum toxin poisoned mammalian neuromuscular junctions. Proc. R. Soc. Lond. B 215; 63–74, 1982.PubMedCrossRefGoogle Scholar
  7. Cooke, J.D. and D.M.J. Quastel. Transmitter release by mammalian motor nerve terminals in response to focal polarization. J. Physiol. 228: 377–405, 1973.PubMedGoogle Scholar
  8. Cull-Candy, S.G., Lundh, H., Thesleff, S. Effects of botulinum toxin on neuromuscular transmission in the rat. J. Physiol. 260: 177–203, 1976.PubMedGoogle Scholar
  9. del Castillo, J. and B. Katz. La base ‘quantale’ de la transmission neuro-musculaire. In: ‘Microphysiologie Comparée des éléments excitables’. Coll. Internat. C.N.R.S. Paris No. 67: 245–258, 1957.Google Scholar
  10. Dennis, M.J. and R. Miledi. Non-transmitting neuromuscular junctions during an early stage of end-plate reinnervation. J. Physiol. 239: 553–570, 1974a.PubMedGoogle Scholar
  11. Dennis, M.J. and R. Miledi. Characteristics of transmitter release at regenerating frog neuromuscular junctions. J. Physiol. 239: 571–594, 1974b.PubMedGoogle Scholar
  12. Duchen, L.W. and D.E. Tonge. The effects of tetanus toxin on neuromuscular transmission and on the morphology of motor end-plate in slow and fast skeletal muscle of the mouse. J. Physiol. 228: 157–172, 1973.PubMedGoogle Scholar
  13. Erxleben, C., G. Carlson and M.E. Kriebel. Studies of miniature endplate currents show that the quantum of release is composed of subunits. Neuroscience Abstracts, 1983.Google Scholar
  14. Erxleben, C. and M.E. Kriebel. Characteristics of miniature and sub-miniature endplate currents at the mouse diaphragm endplate. Naunyn-Schmiedeberg’s Arch, of Pharmacology. Suppl. to Vol. 322, R. 62, 1983.Google Scholar
  15. Fatt, P. and B. Katz. Spontaneous subthreshold activity at motor nerve endings. J. Physiol. 117: 109–128, 1952.PubMedGoogle Scholar
  16. Gross, C.E. and M.E. Kriebel. Multimodal distribution of MEPP amplitudes: the changing distribution with dener-vation, nerve stimulation and high frequencies of spontaneous release. J. Gen. Physiol. 62: 658–659, 1973.Google Scholar
  17. Hanna, R. and M.E. Kriebel. Relationship between synaptic vesicles and miniature endplate potentials in adult and neonatal mouse diaphragm. Neuroscience Abstracts, 1983.Google Scholar
  18. Harris, A.J. and R. Miledi. The effect of type D botulinum toxin on frog neuromuscular junction. J. Physiol. 217: 497–515, 1971.PubMedGoogle Scholar
  19. Heuser, J. and R. Miledi. Effect of lanthanum ions on function and structure of frog neuromuscular junctions. Proc. R. Soc. Lond. B 179: 247–260, 1971.PubMedCrossRefGoogle Scholar
  20. Heuser, J.E., T.S. Reese, M.J. Dennis, Y. Jan, L. Jan and L. Evans. Synaptic vesicle exocytosis captured by quick freezing and correlated with quastal transmitter release. 0. Cell Biol. 81: 275–300, 1979.CrossRefGoogle Scholar
  21. Heuser, J.E., T.S. Reese and D.M.D. Landis. Functional changes in frog neuromuscular junctions studied with freeze-fracture. J. Neurocytology 3: 109–131, 1974.CrossRefGoogle Scholar
  22. Katz, B. The transmission of impulses from nerve to muscle, and the subcellular unit of synaptic action. Proc. R. Soc. B 155: 455–477, 1962.CrossRefGoogle Scholar
  23. Katz, B. “Prologue”, In: Synapses, eds. G.A. Cottrell and P.N.R. Usherwood. Academic Press. 1977. Chapter 1, pp. 1–5.Google Scholar
  24. Katz, B. and R. Miledi. Estimates of quantal content during ‘chemical potentiation’ of transmitter relese. Proc. R. Soc. Lond. B 205; 369–378, 1979.PubMedCrossRefGoogle Scholar
  25. Katz, B. and S. Thesleff. On the factors which determine the amplitude of the ‘miniature end-plate potential’. J. Physiol. 137: 267–278, 1957.PubMedGoogle Scholar
  26. Kelly, S.S. and N. Robbins. Bimodal miniature and evoked end-plate potentials in adult mouse neuromuscular junctions. J. Physiol. 346; 353–363, 1984.PubMedGoogle Scholar
  27. Kidokoro, Y. Two types of miniature endplate potentials in Xenopus nerve-muscle cultures. Neuroscience Research 1: 157–170, 1984.PubMedCrossRefGoogle Scholar
  28. Kita, H. and W. Van der Kloot. Effects of the ionophore X-537A on acetylcholine release at the frog neuromuscular junction. J. Physiol. 259: 177–198, 1976.PubMedGoogle Scholar
  29. Kriebel, M.E. Small mode miniature endplate potentials are increased and evoked in fatigued preparations and in high Mg2+ saline. Brain Research 148: 381–388, 1978.PubMedCrossRefGoogle Scholar
  30. Kriebel, M.E. and E. Florey. Effect of lanthanum ions on the amplitude distributions of miniature endplate potentials and on synaptic vesicles in frog neuromuscular junctions. Neuroscience 9: 535–547, 1983.PubMedCrossRefGoogle Scholar
  31. Kriebel, M.E. and C.E. Gross. Multimodal distribution of frog miniature endplate potentials in adult, denervated, and tadpole leg muscle. J. Gen. Physiol. 64: 85–103, 1974.PubMedCrossRefGoogle Scholar
  32. Kriebel, M.E., R.B. Hanna and G.D. Pappas. Spontaneous potentials and fine structure of identified frog denervated neuromuscular junctions. Neuroscience 5; 97–108, 1980.PubMedCrossRefGoogle Scholar
  33. Kriebel, M.E., F. Llados and C.G. Carlson. Effect of the Ca++ ionophore X-537A and a heat challenge on the distribution of mouse MEPP amplitude histograms. J. Physiol. Paris 76; 435–441, 1980.Google Scholar
  34. Kriebel, M.E., F. Llados and D.R. Matteson. Spontaneous subminiature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release. J. Physiol. 262: 553–581, 1976.PubMedGoogle Scholar
  35. Kriebel, M.E., F. Llados and D.R. Matteson. Histograms of the unitary evoked potential of the mouse diaphragm show multiple peaks. J. Physiol. 322: 211–222, 1982.PubMedGoogle Scholar
  36. Kriebel, M.E. and D.R. Stolper. Non-Poisson distribution in time of small-and large-mode miniature end-plate potentials. Am. J. Physiol. 229: 1321–1329, 1975.PubMedGoogle Scholar
  37. Land, B.R., E.E. Salpeter, M.M. Salpeter. Acetylcholine receptor site density affects the rising phase of miniature endplate currents. Proc. Natl. Acad. Sci. U.S.A. 77(6): 3736–3740, 1980.PubMedCrossRefGoogle Scholar
  38. Llados, F., M.E. Kriebel and D.R. Matteson. ß-Bungarotoxin preferentially blocks one class of miniature endplate potentials. Brain Research 192; 598–602, 1980.PubMedCrossRefGoogle Scholar
  39. Magleby, K.L. and D.C. Miller. Is the quantum of transmitter release composed of subunits A critical analysis in the mouse and frog. J. Physiol. 311: 267–287, 1981.PubMedGoogle Scholar
  40. Magleby, K.L. and M.M. Weinstock. Nickel and calcium ions modify the characteristics of the acetylcholine receptor-channel complex at the frog neuromuscular junction. J. Physiol. 299: 203–218, 1980.PubMedGoogle Scholar
  41. Matteson, D.R., M.E. Kriebel and F. Llados. A statistical model supports the subunit hypothesis of quantal release. Neuroscience Letters 15: 147–152, 1979.PubMedCrossRefGoogle Scholar
  42. Matteson, D.R., F. Llados and M.E. Kriebel. A statistical model indicates that miniature endplate potentials and unitary evoked endplate potentials are composed of subunits. J. Theort. Biol. 90: 337–363, 1981.CrossRefGoogle Scholar
  43. Matthews-Bellinger, J.A. and M.M. Salpeter. Fine structural distribution of acetylcholine receptors at developing mouse neuromuscular junctions. J. Neuroscience 3: 644–657, 1983.Google Scholar
  44. McLarnon, J.G. and D.M.J. Quastel. Postsynaptic effects of magnesium and calcium at the mouse neuromuscular junction. J. Neuroscience 3: 1626–1633, 1983.Google Scholar
  45. Molgó, J. and S. Thesleff. 4-Aminoquinoline-induced ‘giant’ miniature endplate potentials at mammalian neuromuscular junctions. Proc. R. Soc. Lond. B 214: 229–247, 1982.PubMedCrossRefGoogle Scholar
  46. Muniak, C.G., M.E. Kriebel and CG. Carlson. Changes in MEPP and EPP amplitude distributions in the mouse diaphragm during synapse formation and degeneration. Devel. Brain Research 5: 123–138, 1982.CrossRefGoogle Scholar
  47. Sellin, L.C. and S. Thesleff. Pre-and post-synaptic actions of botulinum toxin at the rat neuromuscular junction. J. Physiol. Lond. 317: 487–495, 1981.PubMedGoogle Scholar
  48. Thesleff, S. Supersensitivity of skeletal muscle produced by botulinum toxin. J. Physiol. 151: 598–607, 1960.PubMedGoogle Scholar
  49. Thesleff, S., J. Molgö and H. Lundh. Botulinum toxin and 4-aminoquinoline induce a similar abnormal type of spontaneous quantal transmitter release at the rat neuromuscular junction. Brain Research 264: 89–97, 1983.PubMedCrossRefGoogle Scholar
  50. Tonge, D.A. Physiological characteristics of re-innervation of skeletal muscle in the mouse. J. Physiol. 241: 141–153, 1974.PubMedGoogle Scholar
  51. Vautrin, J. et J. Mambrini. Caractéristiques du potentiel unitaire de plaque motrice de la grenouille. J. Physiol., Paris 77: 999–1010, 1981.Google Scholar
  52. Wernig, A. and I. Motelica-Heino. On the presynaptic nature of the quantal subunit. Neuroscience Letters 8: 231–234, 1978.PubMedCrossRefGoogle Scholar
  53. Wernig, A. and H. Stirner. Quantum amplitude distributions point to functional unity of the synaptic ‘active zone’. Nature, Lond. 269: 820–822, 1977.CrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1986

Authors and Affiliations

  • M. E. Kriebel
  • C. Erxleben

There are no affiliations available

Personalised recommendations