Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1973 Jan;228(2):407–434. doi: 10.1113/jphysiol.1973.sp010093

Cumulative and persistent effects of nerve terminal depolarization on transmitter release

J D Cooke, D M J Quastel
PMCID: PMC1331304  PMID: 4346992

Abstract

1. Following focal depolarization of rat motor nerve terminals there could often be observed an `after-discharge' of m.e.p.p.s with transient frequencies of up to 1000/sec. This after-discharge was graded with intensity and duration of the previous depolarization.

2. Following pulses which were relatively short (about 1 sec) and not too large (< —100 mV local extracellular potential field) the logarithm of m.e.p.p. frequency fell exponentially. With larger or longer pulses there was a tail to the after-discharge which could persist for several minutes.

3. M.e.p.p. frequency during an after-discharge was not inhibited appreciably by nerve terminal hyperpolarization, raised [Ca] (8 mM) or lowered pH.

4. Measured as a multiplication of spontaneous m.e.p.p. frequency after-discharge was depressed in solution containing no Ca2+ and added 1 mM-MgEDTA but equal in 0·125 mM-Ca2+ or 2 mM-Sr2+ to that in 2 mM-Ca2+ or 8 mM-Ca2+.

5. During an after-discharge the multiplication of m.e.p.p. frequency by focal nerve terminal depolarization or raised K+ was reduced. This phenomenon was termed `uncoupling'.

6. It was concluded that the after-discharge is not caused by a persistent rise of K+ concentration in the synaptic cleft, nor by a maintained nerve terminal depolarization.

7. In preparations depolarized by raised K+ m.e.p.p. frequency during a relatively small focal depolarizing pulse rose continuously, after an initial rapid rise, and after the pulse there was a tail of increased m.e.p.p. frequency. The magnitude of the rise during the pulse and the tail after it were similar on, a logarithmic basis; during both processes the logarithm of m.e.p.p. frequency usually followed (approximately) an exponential time course.

8. The relative magnitude of the slow effect of depolarization, as compared with the fast effect, was increased by lowering [Ca] or increasing [Mg], and the slow effect of depolarization in contrast to the fast effect was found to exist in the presence of Ca reduced to about 10-7 M, but only during pulses. At this [Ca] there was no rapid response to depolarization. At [Ca] about 10-10 M, there was no response at all of m.e.p.p. frequency to nerve terminal depolarization.

9. The results are discussed, and compared with similar data referring to `facilitation' and `post-tetanic potentiation'. It is concluded that these and the slow effect of depolarization represent the same phenomenon, a response of the transmitter release system which can be distinguished from the fast response in terms of ionic requirement as well as time course.

Full text

PDF
407

Selected References

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

  1. 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]
  2. Blioch Z. L., Glagoleva I. M., Liberman E. A., Nenashev V. A. A study of the mechanism of quantal transmitter release at a chemical synapse. J Physiol. 1968 Nov;199(1):11–35. doi: 10.1113/jphysiol.1968.sp008637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bloedel J., Gage P. W., Llinás R., Quastel D. M. Transmitter release at the squid giant synapse in the presence of tetrodotoxin. Nature. 1966 Oct 1;212(5057):49–50. doi: 10.1038/212049a0. [DOI] [PubMed] [Google Scholar]
  4. Cooke J. D., Okamoto K., Quastel D. M. The role of calcium in depolarization-secretion coupling at the motor nerve terminal. J Physiol. 1973 Jan;228(2):459–497. doi: 10.1113/jphysiol.1973.sp010095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cooke J. D., Quastel D. M. The specific effect of potassium on transmitter release by motor nerve terminals and its inhibition by calcium. J Physiol. 1973 Jan;228(2):435–458. doi: 10.1113/jphysiol.1973.sp010094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Elmqvist D., Quastel D. M. A quantitative study of end-plate potentials in isolated human muscle. J Physiol. 1965 Jun;178(3):505–529. doi: 10.1113/jphysiol.1965.sp007639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. HUBBARD J. I. REPETITIVE STIMULATION AT THE MAMMALIAN NEUROMUSCULAR JUNCTION, AND THE MOBILIZATION OF TRANSMITTER. J Physiol. 1963 Dec;169:641–662. doi: 10.1113/jphysiol.1963.sp007286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HUGHES J. R. Post-tetanic potentiation. Physiol Rev. 1958 Jan;38(1):91–113. doi: 10.1152/physrev.1958.38.1.91. [DOI] [PubMed] [Google Scholar]
  13. Hubbard J. I., Jones S. F., Landau E. M. On the mechanism by which calcium and magnesium affect the spontaneous release of transmitter from mammalian motor nerve terminals. J Physiol. 1968 Feb;194(2):355–380. doi: 10.1113/jphysiol.1968.sp008413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Katz B., Miledi R. A study of synaptic transmission in the absence of nerve impulses. J Physiol. 1967 Sep;192(2):407–436. doi: 10.1113/jphysiol.1967.sp008307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Katz B., Miledi R. Tetrodotoxin-resistant electric activity in presynaptic terminals. J Physiol. 1969 Aug;203(2):459–487. doi: 10.1113/jphysiol.1969.sp008875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Landau E. M. The interaction of presynaptic polarization with calcium and magnesium in modifying spontaneous transmitter release from mammalian motor nerve terminals. J Physiol. 1969 Aug;203(2):281–299. doi: 10.1113/jphysiol.1969.sp008864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maeno T., Edwards C. Neuromuscular facilitation with low-frequency stimulation and effects of some drugs. J Neurophysiol. 1969 Sep;32(5):785–792. doi: 10.1152/jn.1969.32.5.785. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Quastel D. M., Hackett J. T., Cooke J. D. Calcium: is it required for transmitter secretion? Science. 1971 Jun 4;172(3987):1034–1036. doi: 10.1126/science.172.3987.1034. [DOI] [PubMed] [Google Scholar]
  24. Rahamimoff R. A dual effect of calcium ions on neuromuscular facilitation. J Physiol. 1968 Mar;195(2):471–480. doi: 10.1113/jphysiol.1968.sp008468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weinreich D. Post-tetanic potentiation at the neuromuscular junction of the frog in the presence of tetrodotoxin. Brain Res. 1970 Feb 3;17(3):527–529. doi: 10.1016/0006-8993(70)90262-3. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES