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. 1981 May 1;77(5):503–529. doi: 10.1085/jgp.77.5.503

Changes in miniature endplate potential frequency during repetitive nerve stimulation in the presence of Ca2+, Ba2+, and Sr2+ at the frog neuromuscular junction

PMCID: PMC2215441  PMID: 6262429

Abstract

Miniature endplate potentials (MEPPs) were recorded from frog sartorious neuromuscular junctions under conditions of reduced quantal contents to study the effect of repetitive nerve stimulation on asynchronous (tonic) quantal transmitter release. MEPP frequency increased during repetitive stimulation and then decayed back to the control level after the conditioning trains. The decay of the increased MEPP frequency after 100-to 200-impulse conditioning trains can be described by four components that decayed exponentially with time constants of about 50 ms, 500 ms, 7 s, and 80 s. These time constants are similar to those for the decay of stimulation-induced changes in synchronous (phasic) transmitter release, as measured by endplate potential (EPP) amplitudes, corresponding, respectively, to the first and second components of facilitation, augmentation, and potentiation. The addition of small amounts of Ca2+ or Ba2+ to the Ca2+-containing bathing solution, or the replacement of Ca2+ with Sr2+, led to a greater increase in the stimulation-induced increases in MEPP frequency. The Sr-induced increase in MEPP frequency was associated with an increase in the second component of facilitation of MEPP frequency; the Ba-induced increase with an increase in augmentation. These effects of Sr2+ and Ba2+ on stimulation-induced changes in MEPP frequency are similar to the effects of these ions on stimulation- induced changes in EPP amplitude. These ionic similarities and the similar kinetics of decay suggest that stimulation induced changes in MEPP frequency and EPP amplitude have some similar underlying mechanisms. Calculations are presented which show that a fourth power residual calcium model for stimulation-induced changes in transmitter release cannot readily account for the observation that stimulation- induced changes in MEPP frequency and EPP amplitude have similar time- courses.

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Selected References

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  1. Ahmed Z., Connor J. A. Measurement of calcium influx under voltage clamp in molluscan neurones using the metallochromic dye arsenazo III. J Physiol. 1979 Jan;286:61–82. doi: 10.1113/jphysiol.1979.sp012607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atwood H. L., Swenarchuk L. E., Gruenwald C. R. Long-term synaptic facilitation during sodium accumulation in nerve terminals. Brain Res. 1975 Dec 12;100(1):198–202. doi: 10.1016/0006-8993(75)90260-7. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Baker P. F., Glitsch H. G. Voltage-dependent changes in the permeability of nerve membranes to calcium and other divalent cations. Philos Trans R Soc Lond B Biol Sci. 1975 Jun 10;270(908):389–409. doi: 10.1098/rstb.1975.0018. [DOI] [PubMed] [Google Scholar]
  5. Baker P. F., Hodgkin A. L., Ridgway E. B. Depolarization and calcium entry in squid giant axons. J Physiol. 1971 Nov;218(3):709–755. doi: 10.1113/jphysiol.1971.sp009641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barrett E. F., Barrett J. N., Botz D., Chang D. B., Mahaffey D. Temperature-sensitive aspects of evoked and spontaneous transmitter release at the frog neuromuscular junction. J Physiol. 1978 Jun;279:253–273. doi: 10.1113/jphysiol.1978.sp012343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Barrett E. F., Stevens C. F. The kinetics of transmitter release at the frog neuromuscular junction. J Physiol. 1972 Dec;227(3):691–708. doi: 10.1113/jphysiol.1972.sp010054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Birks R. I., Cohen M. W. The action of sodium pump inhibitors on neuromuscular transmission. Proc R Soc Lond B Biol Sci. 1968 Jul 9;170(1021):381–399. doi: 10.1098/rspb.1968.0046. [DOI] [PubMed] [Google Scholar]
  9. Blaustein M. P., Ratzlaff R. W., Kendrick N. C., Schweitzer E. S. Calcium buffering in presynaptic nerve terminals. I. Evidence for involvement of a nonmitochondrial ATP-dependent sequestration mechanism. J Gen Physiol. 1978 Jul;72(1):15–41. doi: 10.1085/jgp.72.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Braun M., Schmidt R. F. Potential changes recorded from the frog motor nerve terminal during its activation. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;287(1):56–80. doi: 10.1007/BF00362454. [DOI] [PubMed] [Google Scholar]
  11. Braun M., Schmidt R. F., Zimmermann M. Facilitation at the frog neuromuscular junction during and after repetitive stimulation. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;287(1):41–55. doi: 10.1007/BF00362453. [DOI] [PubMed] [Google Scholar]
  12. Charlton M. P., Bittner G. D. Presynaptic potentials and facilitation of transmitter release in the squid giant synapse. J Gen Physiol. 1978 Oct;72(4):487–511. doi: 10.1085/jgp.72.4.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. DEL CASTILLO J., KATZ B. Statistical factors involved in neuromuscular facilitation and depression. J Physiol. 1954 Jun 28;124(3):574–585. doi: 10.1113/jphysiol.1954.sp005130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dennis M. J., Miledi R. Characteristics of transmitter release at regenerating frog neuromuscular junctions. J Physiol. 1974 Jun;239(3):571–594. doi: 10.1113/jphysiol.1974.sp010583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dodge F. A., Jr, Rahamimoff R. Co-operative action a calcium ions in transmitter release at the neuromuscular junction. J Physiol. 1967 Nov;193(2):419–432. doi: 10.1113/jphysiol.1967.sp008367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Erulkar S. D., Rahamimoff R. The role of calcium ions in tetanic and post-tetanic increase of miniature end-plate potential frequency. J Physiol. 1978 May;278:501–511. doi: 10.1113/jphysiol.1978.sp012320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gage P. W., Hubbard J. I. An investigation of the post-tetanic potentiation of end-plate potentials at a mammalian neuromuscular junction. J Physiol. 1966 May;184(2):353–375. doi: 10.1113/jphysiol.1966.sp007919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gorman A. L., Thomas M. V. Changes in the intracellular concentration of free calcium ions in a pace-maker neurone, measured with the metallochromic indicator dye arsenazo III. J Physiol. 1978 Feb;275:357–376. doi: 10.1113/jphysiol.1978.sp012194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hurlbut W. P., Longenecker H. B., Jr, Mauro A. Effects of calcium and magnesium on the frequency of miniature end-plate potentials during prolonged tetanization. J Physiol. 1971 Dec;219(1):17–38. doi: 10.1113/jphysiol.1971.sp009647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. KATZ B., THESLEFF S. On the factors which determine the amplitude of the miniature end-plate potential. J Physiol. 1957 Jul 11;137(2):267–278. doi: 10.1113/jphysiol.1957.sp005811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katz B., Miledi R. The effect of temperature on the synaptic delay at the neuromuscular junction. J Physiol. 1965 Dec;181(3):656–670. doi: 10.1113/jphysiol.1965.sp007790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Katz B., Miledi R. The role of calcium in neuromuscular facilitation. J Physiol. 1968 Mar;195(2):481–492. doi: 10.1113/jphysiol.1968.sp008469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. LILEY A. W. The quantal components of the mammalian end-plate potential. J Physiol. 1956 Sep 27;133(3):571–587. doi: 10.1113/jphysiol.1956.sp005610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Landau E. M., Smolinsky A., Lass Y. Post-tetanic potentiation and facilitation do not share a common calcium-dependent mechanism. Nat New Biol. 1973 Aug 1;244(135):155–157. doi: 10.1038/newbio244155a0. [DOI] [PubMed] [Google Scholar]
  27. Large W. A., Rang H. P. Factors affecting the rate of incorporation of a false transmitter into mammalian motor nerve terminals. J Physiol. 1978 Dec;285:1–24. doi: 10.1113/jphysiol.1978.sp012553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Linder T. M. Calcium and facilitation at two classes of crustacean neuromuscular synapses. J Gen Physiol. 1973 Jan;61(1):56–73. doi: 10.1085/jgp.61.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. MARTIN A. R., PILAR G. PRESYNAPTIC AND POST-SYNAPTIC EVENTS DURING POST-TETANIC POTENTIATION AND FACILITATION IN THE AVIAN CILIARY GANGLION. J Physiol. 1964 Dec;175:17–30. doi: 10.1113/jphysiol.1964.sp007500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Magleby K. L. The effect of tetanic and post-tetanic potentiation on facilitation of transmitter release at the frog neuromuscular junction. J Physiol. 1973 Oct;234(2):353–371. doi: 10.1113/jphysiol.1973.sp010349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Magleby K. L., Zengel J. E. A dual effect of repetitive stimulation on post-tetanic potentiation of transmitter release at the frog neuromuscular junction. J Physiol. 1975 Feb;245(1):163–182. doi: 10.1113/jphysiol.1975.sp010839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Magleby K. L., Zengel J. E. A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction. J Physiol. 1975 Feb;245(1):183–208. doi: 10.1113/jphysiol.1975.sp010840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Magleby K. L., Zengel J. E. Augmentation: A process that acts to increase transmitter release at the frog neuromuscular junction. J Physiol. 1976 May;257(2):449–470. doi: 10.1113/jphysiol.1976.sp011378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Magleby K. L., Zengel J. E. Long term changes in augmentation, potentiation, and depression of transmitter release as a function of repeated synaptic activity at the frog neuromuscular junction. J Physiol. 1976 May;257(2):471–494. doi: 10.1113/jphysiol.1976.sp011379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Magleby K. L., Zengel J. E. Stimulation-induced factors which affect augmentation and potentiation of trasmitter release at the neuromuscular junction. J Physiol. 1976 Sep;260(3):687–717. doi: 10.1113/jphysiol.1976.sp011539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mallart A., Martin A. R. An analysis of facilitation of transmitter release at the neuromuscular junction of the frog. J Physiol. 1967 Dec;193(3):679–694. doi: 10.1113/jphysiol.1967.sp008388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McLachlan E. M. The effects of strontium and barium ions at synapses in sympathetic ganglia. J Physiol. 1977 May;267(2):497–518. doi: 10.1113/jphysiol.1977.sp011823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mellow A. M., Phillips T. E., Silinsky E. M. On the conductance pathway traversed by strontium in mediating the asynchronous release of acetylcholine by motor nerve impulses. Br J Pharmacol. 1978 Jun;63(2):229–232. doi: 10.1111/j.1476-5381.1978.tb09750.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Miledi R., Thies R. Tetanic and post-tetanic rise in frequency of miniature end-plate potentials in low-calcium solutions. J Physiol. 1971 Jan;212(1):245–257. doi: 10.1113/jphysiol.1971.sp009320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rahamimoff R., Yaari Y. Delayed release of transmitter at the frog neuromuscular junction. J Physiol. 1973 Jan;228(1):241–257. doi: 10.1113/jphysiol.1973.sp010084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Silinsky E. M., Mellow A. M., Phillips T. E. Conventional calcium channel mediates asynchronous acetylcholine release by motor nerve impulses. Nature. 1977 Dec 8;270(5637):528–530. doi: 10.1038/270528a0. [DOI] [PubMed] [Google Scholar]
  42. Silinsky E. M. On the role of barium in supporting the asynchronous release of acetylcholine quanta by motor nerve impulses. J Physiol. 1978 Jan;274:157–171. doi: 10.1113/jphysiol.1978.sp012141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Smith S. J., Zucker R. S. Aequorin response facilitation and intracellular calcium accumulation in molluscan neurones. J Physiol. 1980 Mar;300:167–196. doi: 10.1113/jphysiol.1980.sp013157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Younkin S. G. An analysis of the role of calcium in facilitation at the frog neuromuscular junction. J Physiol. 1974 Feb;237(1):1–14. doi: 10.1113/jphysiol.1974.sp010466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zengel J. E., Magleby K. L. Differential effects of Ba2+, Sr2+, and Ca2+ on stimulation-induced changes in transmitter release at the frog neuromuscular junction. J Gen Physiol. 1980 Aug;76(2):175–211. doi: 10.1085/jgp.76.2.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zengel J. E., Magleby K. L. Transmitter release during repetitive stimulation: selective changes produced by Sr2+ and Ba2+. Science. 1977 Jul 1;197(4298):67–69. doi: 10.1126/science.17160. [DOI] [PubMed] [Google Scholar]
  47. Zucker R. S. Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses. J Physiol. 1974 Aug;241(1):69–89. doi: 10.1113/jphysiol.1974.sp010641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Zucker R. S., Lara-Estrella L. O. Is synaptic facilitation caused by presynaptic spike broadening? Nature. 1979 Mar 1;278(5699):57–59. doi: 10.1038/278057a0. [DOI] [PubMed] [Google Scholar]

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