Pflügers Archiv

, Volume 431, Issue 3, pp 325–334 | Cite as

On the possible origin of “giant or slow-rising” miniature end-plate potentials at the neuromuscular junction

  • L. C. Sellin
  • J. Molgó
  • K. Törnquist
  • B. Hansson
  • S. Thesleff
Original Article

Abstract

Giant or slow-rising miniature end-plate potentials (GMEPPs) caused by vesicular release of acetylcholine (ACh) occur at any time in about 50% of mouse diaphragm neuro muscular junctions, but generally at frequencies less than 0.03 s−1. Their frequency is, unlike that of miniature end-plate potentials (MEPPs), not affected by nerve terminal depolarization. Unlike MEPPs and stimulus-evoked end-plate potentials, GMEPPs have a prolonged time-to-peak and show an increase in time-to-peak with amplitude. By using these differences in amplitude and time course, GMEPPs can be separated from MEPPs. In contrast to MEPPs, GMEPPs are not blocked by botulinum neurotoxin type A. GMEPPs have a greater temperature sensitivity than MEPPs, disappearing at temperatures below 15°C. Long-term paralysis by botulinum toxin and certain drugs which inhibit protein kinase C or affect actin filament polymerization (cytochalasins) enhance the frequency of GMEPPs. End-plate current recordings show that similar postsynaptic ACh receptors are activated by MEPPs and GMEPPs. It is suggested that GMEPPs are not caused by mechanisms involved in “regulated” neurotransmitter release but are generated by “constitutive secretion”.

Key words

Neurotransmitter release Constitutive secretion Miniature end-plate potentials Giant miniature end-plate potentials Protein kinase C 

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References

  1. 1.
    Alkadhi KA (1987) Effects of emetine and dehydroemetine at the frog neuromuscular junction. Eur J Pharmacol 138:257–264PubMedGoogle Scholar
  2. 2.
    Alkadhi KA (1989) Giant miniature end-plate potentials at the untreated and emetine-treated frog neuromuscular junction. J Physiol (Lond) 412:475–491Google Scholar
  3. 3.
    Bauerfeind R, Régnier-Vigouroux A, Flatmark T, Huttner WB (1993) Selective storage of acetylcholine, but not catecholamines, in neuroendocrine synaptic-like microvesicles of early endosomal origin. Neuron 11:105–121PubMedGoogle Scholar
  4. 4.
    Bauerfeind R, Huttner WB, Almers W, Augustine GJ (1994) Quantal neurotransmitter release from early endosomes? Trends Cell Biol 4:155–156PubMedGoogle Scholar
  5. 5.
    Bittner MA, Holz RW (1993) Protein kinase C and clostridial neurotoxins affect discrete and related steps in the secretory pathway. Cell Mol Neurobiol 13:649–664PubMedGoogle Scholar
  6. 6.
    Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, DeCamilli P, Südhof TC, Niemann H, Jahn R (1993) Botulinum neurotoxin-A selectively cleaves the synaptic protein SNAP-25. Nature 365:160–163PubMedGoogle Scholar
  7. 7.
    Burgess TL, Kelly RB (1987) Constitutive and regulated secretion of proteins. Annu Rev Cell Biol 3:243–249PubMedGoogle Scholar
  8. 8.
    Cherkivakil R, Ginsburg S, Meiri H, (1995) The difference in shape of spontaneous and uniquantal evoked synaptic potentials in frog muscle. J Physiol (Lond) 482:641–650Google Scholar
  9. 9.
    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 215:63–74PubMedGoogle Scholar
  10. 10.
    Considine RV, Handler CM, Simpson LL, Sherwin JR (1991) Tetanus toxin inhibits neurotensin-induced mobilization of cytosolic protein kinase C in NG-108 cells. Toxicon 29:1351–1357PubMedGoogle Scholar
  11. 11.
    Dan Y, Poo M-M (1992) Quantal transmitter secretion from myocytes loaded with acetylcholine. Nature 359:733–736PubMedGoogle Scholar
  12. 12.
    Dekker LV, De Graan PNE, Gispen WH (1991) Transmitter release: target of regulation by protein kinase C? Prog Brain Res 89:209–233PubMedGoogle Scholar
  13. 13.
    Duchen LW, Strich SJ (1968) The effects of botulinum toxin on the pattern of innervation of skeletal muscle in the mouse. Q J Exp Physiol 53:84–89Google Scholar
  14. 14.
    Girod R, Popov S, Alder J, Zheng JQ, Lohof A, Poo M-M (1995) Spontaneous quantal transmitter secretion from myocytes and fibroblasts: comparison with neural secretion. J Neurosci 15:2826–2838PubMedGoogle Scholar
  15. 15.
    Gundersen K (1990) Spontaneous activity at long-term silenced synapses in rat muscle. J Physiol (Lond) 430:399–418Google Scholar
  16. 16.
    Hannum YA, Bell RM (1988) Aminoacridines, potent inhibitors of protein kinase C. J Biol Chem 263:5124–5131PubMedGoogle Scholar
  17. 17.
    Hartwig JH, Thelen M, Rosen A, Janmey PA, Nairn AC, Aderem A (1992) MARCKS is an actin filament cross-linking protein regulated by protein kinase C and calcium-calmodulin. Nature 356:618–622PubMedGoogle Scholar
  18. 18.
    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
  19. 19.
    Haylett T, Thilo L (1991) Endosome-lysosome fusion at low temperature. J Biol Chem 266:8322–8327PubMedGoogle Scholar
  20. 20.
    Jahn R, Südhof TC (1994) Synaptic vesicles and exocytosis. Annu Rev Neurosci 17:219–246PubMedGoogle Scholar
  21. 21.
    Johnson RG (1987) Cellular and molecular biology of hormone- and neurotransmitter-containing secretory vesicles. Ann NY Acad Sci 493:1–58PubMedGoogle Scholar
  22. 22.
    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
  23. 23.
    Kelly RB (1993 a) Storage and release of neurotransmitter. Neuron [suppl] 10:43–53PubMedGoogle Scholar
  24. 24.
    Kelly RB (1993 b) Secretion. A question of endosomes. Nature 364:537–540PubMedGoogle Scholar
  25. 25.
    Kim YI, Lömo 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
  26. 26.
    Kriebel ME, Llados F, Matteson DR (1982) Histograms of the unitary evoked potential of the mouse diaphragm show multiple peaks. J Physiol (Lond) 322:211–222Google Scholar
  27. 27.
    Liley AW (1957) Spontaneous release of transmitter substance in multiquantal units. J Physiol (Lond) 136:595–605Google Scholar
  28. 28.
    Lupa MT, Tabti N, Thesleff S, Vyskocil F, Yu S-P (1986) The nature and origin of calcium-insensitive miniature end-plate potentials at rodent neuromuscular junctions. J Physiol (Lond) 381:607–618Google Scholar
  29. 29.
    McMahon HT, Foran P, Dolly JO, Verhage M, Weigart VM, Nicholls DG (1992) Tetanus and botulinum toxins type A and B inhibit glutamate, gamma-amino butyric acid, aspartate and met-enkephalin release from synaptosomes. J Biol Chem 267:21238–21242Google Scholar
  30. 30.
    Presek P, Jessen S, Dreyer F, Jarvie PE, Findik D, Dunkley PR (1992) Tetanus toxin inhibits depolarization-stimulated protein phosphorylation in rat cortical synaptosomes: effect on synapsin I phosphorylation and translocation. J Neurochem 59:1336–1343PubMedGoogle Scholar
  31. 31.
    Régnier-Vigouroux A, Tooze SA, Huttner WB (1991) Newly synthesized synaptophysin is transported to synaptic-like microvesicles via constitutive secretory vesicles and the plasma membrane. EMBO J 10:3589–3601PubMedGoogle Scholar
  32. 32.
    Robinson PJ (1992) The role of protein kinase C and its neuronal substrates dephosphin, B-50, and MARCKS in neurotransmitter release. Mol Neurobiol 5:87–130Google Scholar
  33. 33.
    Robinson PJ, Liu J-P, Powell KA, Fykse EM, Südhof TC (1994) Phosphorylation of dynamin I and synaptic-vesicle recycling. Trends Neurosci 17:348–353PubMedGoogle Scholar
  34. 34.
    Sala C, Andreose JS, Fumagalli G, Lömo T (1995) Calcitonin gene-related peptide: possible role in formation and maintenance of neuromuscular junctions. J Neurosci 15:520–528PubMedGoogle Scholar
  35. 35.
    Söllner T, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE (1993) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic docking, activation and fusion. Cell 75:409–418PubMedGoogle Scholar
  36. 36.
    Tabti N, Lupa MT, Yu S-P, Thesleff S (1986) Pharmacological characterization of the calcium-insensitive intermittent acetylcholine release at the rat neuromuscular junction. Acta Physiol Scand 128:429–436PubMedGoogle Scholar
  37. 37.
    Thesleff S, Molgó J (1983) A new type of transmitter release at the neuromuscular junction. Neuroscience 9:1–8PubMedGoogle Scholar
  38. 38.
    Thesleff S, Molgó J, Lundh H (1983) Botulinum toxin and 4-aminoquinoline induce a new type of spontaneous quantal transmitter release at the rat neuromuscular junction. Brain Res 264:89–99PubMedGoogle Scholar
  39. 39.
    Thesleff S, Sellin LC, Tågerud S (1990) Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates. B J Pharmacol 100:487–490Google Scholar
  40. 40.
    Van der Kloot W (1988) Estimating the timing of quantal releases during end-plate currents at the frog neuromuscular junction. J Physiol (Lond) 402:595–603Google Scholar
  41. 41.
    Von Grafenstein H, Borges R, Knight DE (1992) The effect of botulinum toxin type D on the triggered and constitutive exocytosis/endocytosis cycles in cultures of bovine adrenal medullary cells. FEBS Lett 298:118–122PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • L. C. Sellin
    • 1
  • J. Molgó
    • 2
  • K. Törnquist
    • 3
  • B. Hansson
    • 4
  • S. Thesleff
    • 4
  1. 1.Division of Biophysics, Department of Physical SciencesUniversity of OuluOuluFinland
  2. 2.Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRSGif sur Yvette cedexFrance
  3. 3.Department of Biosciences, Division of Animal PhysiologyUniversity of Helsinki and the Minerva Foundation Institute for Medical ResearchHelsinkiFinland
  4. 4.Department of PharmacologyUniversity of LundLundSweden

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