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. 1981 Feb;311:267–287. doi: 10.1113/jphysiol.1981.sp013584

Is the quantum of transmitter release composed of subunits? A critical analysis in the mouse and frog

K L Magleby 1, D C Miller 1,*
PMCID: PMC1275409  PMID: 6267253

Abstract

1. Miniature end-plate potentials (m.e.p.p.s) were recorded from mouse diaphragm and frog cutaneous pectoris muscles and miniature end-plate currents (m.e.p.c.s) were recorded from frog cutaneous pectoris to investigate the proposal that the m.e.p.p. is built up of one to thirty subunits. Evidence for this hypothesis is drawn mainly from the observations that there is a class of m.e.p.p.s smaller than the classical m.e.p.p.s, and that histograms of m.e.p.p. amplitudes display multiple peaks which often appear to be regularly spaced and which extend throughout the histograms; in terms of the subunit hypothesis each successive peak results from an increasing integral number of subunits per m.e.p.p. (Kriebel, Llados & Matteson, 1976; Wernig & Stirner, 1977).

2. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas confirmed the existence of two classes of m.e.p.p.s as reported by Kriebel & Gross (1974): a larger class (well described by a Gaussian curve) which consists of the classical m.e.p.p.s, and a smaller class with amplitudes considerable less than the classical m.e.p.p.s.

3. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas showed multiple peaks that extended throughout the histograms.

4. Autocorrelations of the histograms, an unbiased method used to test for regularity in data, showed that the multiple peaks were not regularly spaced, as required by the subunit hypothesis.

5. A series of computer simulations demonstrated that, for expected levels of base-line noise in the recording system, multiple peaks that extend throughout histograms of m.e.p.p. amplitudes could arise from subunits only if the standard deviation of the subunit amplitude were less than 2-5% of the mean subunit amplitude and the standard deviation of the variability in post-synaptic sensitivity were less than 2% of the mean post-synaptic sensitivity. It seems unlikely that the variability in post-synaptic sensitivity and in proposed subunit amplitude would be as small as this.

6. Taking more realistic estimates for the standard deviation of the subunit amplitude of 12% of the mean subunit amplitude and standard deviation of the variation in post-synaptic sensitivity of 4% of the mean sensitivity, it was found that at most three to four regularly spaced peaks would be apparent in m.e.p.p. amplitude histograms due to subunits.

7. On the basis of these theoretical considerations it seems doubtful that the multiple peaks observed to extend throughout histograms of m.e.p.p. amplitudes could arise from subunits; therefore, the experimental data that have been used to support the subunit hypothesis are unlikely to have arisen from a subunit mechanism.

8. We suggest that there are few, if any, data that directly support the subunit hypothesis. The multiple peaks observed to extend throughout m.e.p.p. amplitude histograms most likely arise from random variation in the data, although additional factors cannot be ruled out.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BOYD I. A., MARTIN A. R. The end-plate potential in mammalian muscle. J Physiol. 1956 Apr 27;132(1):74–91. doi: 10.1113/jphysiol.1956.sp005503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevan S. Sub-miniature end-plate potentials at untreated frog neuromuscular junctions. J Physiol. 1976 Jun;258(1):145–155. doi: 10.1113/jphysiol.1976.sp011411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cooke J. D., Quastel D. M. Transmitter release by mammalian motor nerve terminals in response to focal polarization. J Physiol. 1973 Jan;228(2):377–405. doi: 10.1113/jphysiol.1973.sp010092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cull-Candy S. G., Miledi R., Trautmann A. End-plate currents and acetylcholine noise at normal and myasthenic human end-plates. J Physiol. 1979 Feb;287:247–265. doi: 10.1113/jphysiol.1979.sp012657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DEL CASTILLO J., KATZ B. Quantal components of the end-plate potential. J Physiol. 1954 Jun 28;124(3):560–573. doi: 10.1113/jphysiol.1954.sp005129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dreyer F., Müller K. D., Peper K., Sterz R. The M. omohyoideus of the mouse as a convenient mammalian muscle preparation. A study of junctional and extrajunctional acetylcholine receptors by noise analysis and cooperativity. Pflugers Arch. 1976 Dec 28;367(2):115–122. doi: 10.1007/BF00585146. [DOI] [PubMed] [Google Scholar]
  7. Heuser J. E., Reese T. S., Dennis M. J., Jan Y., Jan L., Evans L. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J Cell Biol. 1979 May;81(2):275–300. doi: 10.1083/jcb.81.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Katz B., Miledi R. Estimates of quantal content during 'chemical potentiation' of transmitter release. Proc R Soc Lond B Biol Sci. 1979 Aug 31;205(1160):369–378. doi: 10.1098/rspb.1979.0070. [DOI] [PubMed] [Google Scholar]
  9. Kriebel M. E., Gross C. E. Multimodal distribution of frog miniature endplate potentials in adult denervated and tadpole leg muscle. J Gen Physiol. 1974 Jul;64(1):85–103. doi: 10.1085/jgp.64.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kriebel M. E., Llados F., Matteson D. R. Spontaneous subminature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release. J Physiol. 1976 Nov;262(3):553–581. doi: 10.1113/jphysiol.1976.sp011610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kriebel M. E. Small mode miniature end plate potentials are increased and evoked in fatigued preparations and in high Mg2+ saline. Brain Res. 1978 Jun 16;148(2):381–388. doi: 10.1016/0006-8993(78)90726-6. [DOI] [PubMed] [Google Scholar]
  12. LILEY A. W. An investigation of spontaneous activity at the neuromuscular junction of the rat. J Physiol. 1956 Jun 28;132(3):650–666. doi: 10.1113/jphysiol.1956.sp005555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LILEY A. W. Spontaneous release of transmitter substance in multiquantal units. J Physiol. 1957 May 23;136(3):595–605. doi: 10.1113/jphysiol.1957.sp005784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. MAMBRINI J., BENOIT P. R. ACTION DU CALCIUM SUR LA JONCTION NEURO-MUSCULAIRE CHEZ LA GRENOUILLE. C R Seances Soc Biol Fil. 1964;158:1454–1458. [PubMed] [Google Scholar]
  15. MARTIN A. R. A further study of the statistical composition on the end-plate potential. J Physiol. 1955 Oct 28;130(1):114–122. doi: 10.1113/jphysiol.1955.sp005397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Magleby K. L., Weinstock M. M. Nickel and calcium ions modify the characteristics of the acetylcholine receptor-channel complex at the frog neuromuscular junction. J Physiol. 1980 Feb;299:203–218. doi: 10.1113/jphysiol.1980.sp013120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matteson D. R., Kreibel M. E., Llados F. A statistical model supports the subunit hypothesis of quantal relsease. Neurosci Lett. 1979 Dec;15(2-3):147–152. doi: 10.1016/0304-3940(79)96104-4. [DOI] [PubMed] [Google Scholar]
  19. Miller D. C., Weinstock M. M., Magleby K. L. Is the quantum of transmitter release composed of subunits? Nature. 1978 Jul 27;274(5669):388–390. doi: 10.1038/274388a0. [DOI] [PubMed] [Google Scholar]
  20. Motelica-Heino I., Wernig A. Further investigation on the quantal subunit at the frog neuromuscular junction [proceedings]. J Physiol. 1978 Nov;284:142P–142P. [PubMed] [Google Scholar]
  21. Neher E., Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature. 1976 Apr 29;260(5554):799–802. doi: 10.1038/260799a0. [DOI] [PubMed] [Google Scholar]
  22. Quastel D. M. Correction of end-plate potentials and currents for nonlinear summation. Can J Physiol Pharmacol. 1979 Jul;57(7):702–709. doi: 10.1139/y79-106. [DOI] [PubMed] [Google Scholar]
  23. Robinson J. Estimation of parameters for a model of transmitter release at synapses. Biometrics. 1976 Mar;32(1):61–68. [PubMed] [Google Scholar]
  24. Wernig A., Stirner H. Quantum amplitude distributions point to functional unity of the synaptic 'active zone'. Nature. 1977 Oct 27;269(5631):820–822. doi: 10.1038/269820a0. [DOI] [PubMed] [Google Scholar]

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