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

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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”.

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References

  1. Alkadhi KA (1987) Effects of emetine and dehydroemetine at the frog neuromuscular junction. Eur J Pharmacol 138:257–264

    PubMed  Google Scholar 

  2. Alkadhi KA (1989) Giant miniature end-plate potentials at the untreated and emetine-treated frog neuromuscular junction. J Physiol (Lond) 412:475–491

    Google Scholar 

  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 11:105–121

    PubMed  Google Scholar 

  4. Bauerfeind R, Huttner WB, Almers W, Augustine GJ (1994) Quantal neurotransmitter release from early endosomes? Trends Cell Biol 4:155–156

    PubMed  Google Scholar 

  5. Bittner MA, Holz RW (1993) Protein kinase C and clostridial neurotoxins affect discrete and related steps in the secretory pathway. Cell Mol Neurobiol 13:649–664

    PubMed  Google Scholar 

  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 365:160–163

    PubMed  Google Scholar 

  7. Burgess TL, Kelly RB (1987) Constitutive and regulated secretion of proteins. Annu Rev Cell Biol 3:243–249

    PubMed  Google Scholar 

  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) 482:641–650

    Google Scholar 

  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 215:63–74

    PubMed  Google Scholar 

  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 29:1351–1357

    PubMed  Google Scholar 

  11. Dan Y, Poo M-M (1992) Quantal transmitter secretion from myocytes loaded with acetylcholine. Nature 359:733–736

    PubMed  Google Scholar 

  12. Dekker LV, De Graan PNE, Gispen WH (1991) Transmitter release: target of regulation by protein kinase C? Prog Brain Res 89:209–233

    PubMed  Google Scholar 

  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 53:84–89

    Google Scholar 

  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 15:2826–2838

    PubMed  Google Scholar 

  15. Gundersen K (1990) Spontaneous activity at long-term silenced synapses in rat muscle. J Physiol (Lond) 430:399–418

    Google Scholar 

  16. Hannum YA, Bell RM (1988) Aminoacridines, potent inhibitors of protein kinase C. J Biol Chem 263:5124–5131

    PubMed  Google Scholar 

  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 356:618–622

    PubMed  Google Scholar 

  18. Hartzell HC, Kuffler SW, Yoshikami D (1975) Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. J Physiol (Lond) 251:427–463

    Google Scholar 

  19. Haylett T, Thilo L (1991) Endosome-lysosome fusion at low temperature. J Biol Chem 266:8322–8327

    PubMed  Google Scholar 

  20. Jahn R, Südhof TC (1994) Synaptic vesicles and exocytosis. Annu Rev Neurosci 17:219–246

    PubMed  Google Scholar 

  21. Johnson RG (1987) Cellular and molecular biology of hormone- and neurotransmitter-containing secretory vesicles. Ann NY Acad Sci 493:1–58

    PubMed  Google Scholar 

  22. Katz B, Thesleff S (1957) On the factors which determine the amplitude of the “miniature end-plate potential”. J Physiol (Lond) 137:267–278

    Google Scholar 

  23. Kelly RB (1993 a) Storage and release of neurotransmitter. Neuron [suppl] 10:43–53

    PubMed  Google Scholar 

  24. Kelly RB (1993 b) Secretion. A question of endosomes. Nature 364:537–540

    PubMed  Google Scholar 

  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) 356:587–599

    Google Scholar 

  26. Kriebel ME, Llados F, Matteson DR (1982) Histograms of the unitary evoked potential of the mouse diaphragm show multiple peaks. J Physiol (Lond) 322:211–222

    Google Scholar 

  27. Liley AW (1957) Spontaneous release of transmitter substance in multiquantal units. J Physiol (Lond) 136:595–605

    Google Scholar 

  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) 381:607–618

    Google Scholar 

  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 267:21238–21242

    Google Scholar 

  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 59:1336–1343

    PubMed  Google Scholar 

  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 10:3589–3601

    PubMed  Google Scholar 

  32. Robinson PJ (1992) The role of protein kinase C and its neuronal substrates dephosphin, B-50, and MARCKS in neurotransmitter release. Mol Neurobiol 5:87–130

    Google Scholar 

  33. Robinson PJ, Liu J-P, Powell KA, Fykse EM, Südhof TC (1994) Phosphorylation of dynamin I and synaptic-vesicle recycling. Trends Neurosci 17:348–353

    PubMed  Google Scholar 

  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 15:520–528

    PubMed  Google Scholar 

  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 75:409–418

    PubMed  Google Scholar 

  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 128:429–436

    PubMed  Google Scholar 

  37. Thesleff S, Molgó J (1983) A new type of transmitter release at the neuromuscular junction. Neuroscience 9:1–8

    PubMed  Google Scholar 

  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 264:89–99

    PubMed  Google Scholar 

  39. Thesleff S, Sellin LC, Tågerud S (1990) Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates. B J Pharmacol 100:487–490

    Google Scholar 

  40. Van der Kloot W (1988) Estimating the timing of quantal releases during end-plate currents at the frog neuromuscular junction. J Physiol (Lond) 402:595–603

    Google Scholar 

  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 298:118–122

    PubMed  Google Scholar 

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Sellin, L.C., Molgó, J., Törnquist, K. et al. On the possible origin of “giant or slow-rising” miniature end-plate potentials at the neuromuscular junction. Pflugers Arch. 431, 325–334 (1996). https://doi.org/10.1007/BF02207269

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  • DOI: https://doi.org/10.1007/BF02207269

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