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. 1995 Jul;69(1):148–154. doi: 10.1016/S0006-3495(95)79884-8

The rise times of miniature endplate currents suggest that acetylcholine may be released over a period of time.

W Van der Kloot 1
PMCID: PMC1236233  PMID: 7669892

Abstract

Models of miniature endplate currents predict 20-80% rise times of 100 microseconds or less. These predictions are substantially less than most of the rise times recorded in the literature. New measurements were made of rise times at the frog neuromuscular junction using extracellular recording. The mean 20-80% rise time was 250 microseconds. Rise times were variable; at 20 degrees C, 95% of them fell in a range from 140 to 460 microseconds. The most questionable assumption in the models is that the acetylcholine (ACh) is released instantaneously. Modifying the model, so that ACh diffuses from the vesicle through a pore, lengthens the rise time to observed levels. It has been proposed that ACh is released from the vesicle in exchange for Na+. However, the rise times of miniature endplate currents recorded in solutions in which the Na+ is replaced by sucrose are in the normal range. The Q10 for the rise of miniature endplate currents is approximately 2, which is consistent with the models and with temperature effects on pore formation in mast cells.

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Selected References

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

  1. Almers W., Breckenridge L. J., Iwata A., Lee A. K., Spruce A. E., Tse F. W. Millisecond studies of single membrane fusion events. Ann N Y Acad Sci. 1991;635:318–327. doi: 10.1111/j.1749-6632.1991.tb36502.x. [DOI] [PubMed] [Google Scholar]
  2. Anglister L., Stiles J. R., Salpeter M. M. Acetylcholinesterase density and turnover number at frog neuromuscular junctions, with modeling of their role in synaptic function. Neuron. 1994 Apr;12(4):783–794. doi: 10.1016/0896-6273(94)90331-x. [DOI] [PubMed] [Google Scholar]
  3. Barrett E. F., Stevens C. F. Quantal independence and uniformity of presynaptic release kinetics at the frog neuromuscular junction. J Physiol. 1972 Dec;227(3):665–689. doi: 10.1113/jphysiol.1972.sp010053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bartol T. M., Jr, Land B. R., Salpeter E. E., Salpeter M. M. Monte Carlo simulation of miniature endplate current generation in the vertebrate neuromuscular junction. Biophys J. 1991 Jun;59(6):1290–1307. doi: 10.1016/S0006-3495(91)82344-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bekkers J. M., Richerson G. B., Stevens C. F. Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5359–5362. doi: 10.1073/pnas.87.14.5359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen I. S., Van der Kloot W. Effects of low temperature and terminal membrane potential on quantal size at frog neuromuscular junction. J Physiol. 1983 Mar;336:335–344. doi: 10.1113/jphysiol.1983.sp014584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen I., van der Kloot W., Attwell D. The timing of channel opening during miniature end-plate currents. Brain Res. 1981 Oct 26;223(1):185–189. doi: 10.1016/0006-8993(81)90821-0. [DOI] [PubMed] [Google Scholar]
  8. Colquhoun D., Large W. A., Rang H. P. An analysis of the action of a false transmitter at the neuromuscular junction. J Physiol. 1977 Apr;266(2):361–395. doi: 10.1113/jphysiol.1977.sp011772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Dudel J. Control of quantal transmitter release at frog's motor nerve terminals. II. Modulation by de- or hyperpolarizing pulses. Pflugers Arch. 1984 Nov;402(3):235–243. doi: 10.1007/BF00585505. [DOI] [PubMed] [Google Scholar]
  11. Dwyer T. M. The rising phase of the miniature endplate current at the frog neuromuscular junction. Biochim Biophys Acta. 1981 Aug 6;646(1):51–60. doi: 10.1016/0005-2736(81)90271-6. [DOI] [PubMed] [Google Scholar]
  12. FATT P., KATZ B. Spontaneous subthreshold activity at motor nerve endings. J Physiol. 1952 May;117(1):109–128. [PMC free article] [PubMed] [Google Scholar]
  13. Gage P. W. Generation of end-plate potentials. Physiol Rev. 1976 Jan;56(1):177–247. doi: 10.1152/physrev.1976.56.1.177. [DOI] [PubMed] [Google Scholar]
  14. Gage P. W., McBurney R. N. Effects of membrane potential, temperature and neostigmine on the conductance change caused by a quantum or acetylcholine at the toad neuromuscular junction. J Physiol. 1975 Jan;244(2):385–407. doi: 10.1113/jphysiol.1975.sp010805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gage P. W., Van Helden D. Effects of permeant monovalent cations on end-plate channels. J Physiol. 1979 Mar;288:509–528. [PMC free article] [PubMed] [Google Scholar]
  16. Head S. D. Temperature and end-plate currents in rat diaphragm. J Physiol. 1983 Jan;334:441–459. doi: 10.1113/jphysiol.1983.sp014505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KATZ B., MILEDI R. THE MEASUREMENT OF SYNAPTIC DELAY, AND THE TIME COURSE OF ACETYLCHOLINE RELEASE AT THE NEUROMUSCULAR JUNCTION. Proc R Soc Lond B Biol Sci. 1965 Feb 16;161:483–495. doi: 10.1098/rspb.1965.0016. [DOI] [PubMed] [Google Scholar]
  18. Katz B., Miledi R. Spontaneous and evoked activity of motor nerve endings in calcium Ringer. J Physiol. 1969 Aug;203(3):689–706. doi: 10.1113/jphysiol.1969.sp008887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katz B., Miledi R. The binding of acetylcholine to receptors and its removal from the synaptic cleft. J Physiol. 1973 Jun;231(3):549–574. doi: 10.1113/jphysiol.1973.sp010248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Khanin R., Parnas H., Segel L. Diffusion cannot govern the discharge of neurotransmitter in fast synapses. Biophys J. 1994 Sep;67(3):966–972. doi: 10.1016/S0006-3495(94)80562-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Land B. R., Salpeter E. E., Salpeter M. M. Acetylcholine receptor site density affects the rising phase of miniature endplate currents. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3736–3740. doi: 10.1073/pnas.77.6.3736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lederer W. J., Spindler A. J., Eisner D. A. Thick slurry bevelling: a new technique for bevelling extremely fine microelectrodes and micropipettes. Pflugers Arch. 1979 Sep;381(3):287–288. doi: 10.1007/BF00583261. [DOI] [PubMed] [Google Scholar]
  23. Madsen B. W., Edeson R. O., Lam H. S., Milne R. K. Numerical simulation of miniature endplate currents. Neurosci Lett. 1984 Jul 13;48(1):67–74. doi: 10.1016/0304-3940(84)90290-8. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Miledi R., Nakajima S., Parker I. Endplate currents in sucrose solution. Proc R Soc Lond B Biol Sci. 1980 Dec 31;211(1182):135–141. doi: 10.1098/rspb.1980.0161. [DOI] [PubMed] [Google Scholar]
  26. Monck J. R., Fernandez J. M. The exocytotic fusion pore. J Cell Biol. 1992 Dec;119(6):1395–1404. doi: 10.1083/jcb.119.6.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nanavati C., Fernandez J. M. The secretory granule matrix: a fast-acting smart polymer. Science. 1993 Feb 12;259(5097):963–965. doi: 10.1126/science.8438154. [DOI] [PubMed] [Google Scholar]
  28. Nigmatullin N. R., Snetkov V. A., Nikol'skii E. E., Magazanik L. G. Analiz modeli miniatiurnogo toka kontsevoi plastinki. Neirofiziologiia. 1988;20(3):390–398. [PubMed] [Google Scholar]
  29. Oberhauser A. F., Monck J. R., Fernandez J. M. Events leading to the opening and closing of the exocytotic fusion pore have markedly different temperature dependencies. Kinetic analysis of single fusion events in patch-clamped mouse mast cells. Biophys J. 1992 Mar;61(3):800–809. doi: 10.1016/S0006-3495(92)81884-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Parnas H., Flashner M., Spira M. E. Sequential model to describe the nicotinic synaptic current. Biophys J. 1989 May;55(5):875–884. doi: 10.1016/S0006-3495(89)82886-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Parnas H., Parnas I., Segel L. A. On the contribution of mathematical models to the understanding of neurotransmitter release. Int Rev Neurobiol. 1990;32:1–50. doi: 10.1016/s0074-7742(08)60579-6. [DOI] [PubMed] [Google Scholar]
  32. Rosenberry T. L. Quantitative simulation of endplate currents at neuromuscular junctions based on the reaction of acetylcholine with acetylcholine receptor and acetylcholinesterase. Biophys J. 1979 May;26(2):263–289. doi: 10.1016/S0006-3495(79)85249-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Spruce A. E., Breckenridge L. J., Lee A. K., Almers W. Properties of the fusion pore that forms during exocytosis of a mast cell secretory vesicle. Neuron. 1990 May;4(5):643–654. doi: 10.1016/0896-6273(90)90192-i. [DOI] [PubMed] [Google Scholar]
  34. Van der Kloot W., Balezina O. P., Molgó J., Naves L. A. The timing of channel opening during miniature endplate currents at the frog and mouse neuromuscular junctions: effects of fasciculin-2, other anti-cholinesterases and vesamicol. Pflugers Arch. 1994 Sep;428(2):114–126. doi: 10.1007/BF00374848. [DOI] [PubMed] [Google Scholar]
  35. Van der Kloot W., Cohen I. S. Temperature effects on spontaneous and evoked quantal size at the frog neuromuscular junction. J Neurosci. 1984 Sep;4(9):2200–2203. doi: 10.1523/JNEUROSCI.04-09-02200.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Van der Kloot W., Molgó J. Quantal acetylcholine release at the vertebrate neuromuscular junction. Physiol Rev. 1994 Oct;74(4):899–991. doi: 10.1152/physrev.1994.74.4.899. [DOI] [PubMed] [Google Scholar]
  37. Van der Kloot W. Pretreatment with hypertonic solutions increases quantal size at the frog neuromuscular junction. J Neurophysiol. 1987 May;57(5):1536–1554. doi: 10.1152/jn.1987.57.5.1536. [DOI] [PubMed] [Google Scholar]
  38. Van der Kloot W. Statistical and graphical methods for testing the hypothesis that quanta are made up of subunits. J Neurosci Methods. 1989 Feb;27(1):81–89. doi: 10.1016/0165-0270(89)90054-x. [DOI] [PubMed] [Google Scholar]
  39. Van der Kloot W. The regulation of quantal size. Prog Neurobiol. 1991;36(2):93–130. doi: 10.1016/0301-0082(91)90019-w. [DOI] [PubMed] [Google Scholar]
  40. Wathey J. C., Nass M. M., Lester H. A. Numerical reconstruction of the quantal event at nicotinic synapses. Biophys J. 1979 Jul;27(1):145–164. doi: 10.1016/S0006-3495(79)85208-X. [DOI] [PMC free article] [PubMed] [Google Scholar]

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