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. 1982;328:547–562. doi: 10.1113/jphysiol.1982.sp014283

Effects of calcium and strontium in the process of acetylcholine release from motor nerve endings

A M Mellow 1, B D Perry 1, E M Silinsky 1,*
PMCID: PMC1225677  PMID: 6982330

Abstract

1. The effects of Ca and Sr ions on synchronous acetyleholine (ACh) secretion (the impulsive, physiologically functional form of secretion which produces an end-plate potential in response to a single nerve impulse) and on asynchronous ACh secretion (the delayed, residual increase in miniature end-plate potential frequency evoked by repetitive nerve impulses or by accumulation of intracellular divalent cations) were studied at frog neuromuscular junctions.

2. In a comparison of their extracellular effects, Ca was far more effective than Sr in supporting synchronous ACh secretion but less effective than Sr in mediating asynchronous release evoked by repetitive nerve impulses.

3. In studies of their intracellular effects, Sr and Ca were delivered to the nerve terminal cytoplasm using liposomes as a vehicle. Ca-containing liposomes, although producing effects on asynchronous ACh secretion that were indistinguishable from those of equimolar Sr-containing liposomes, were more effective than Sr-containing liposomes in increasing synchronous release.

4. Extracellular Ca behaved as a potent competitve inhibitor of asynchronous, neurally evoked release mediated by Sr. In contrast, intracellular Ca (i.e. liposomal Ca), whilst increasing synchronous ACh release, failed to antagonize evoked asynchronous release.

5. The results demonstrate that synchronous and asynchronous secretion have different sensitivities to alterations in intracellular divalent cation concentrations. It is suggested that selectivity for Ca over Sr may occur at intraterminal sites responsible for synchronous ACh secretion but not at sites responsible for asynchronous ACh release. Furthermore, Ca appears to bind with high affinity as an antagonist at the external surface of the nerve ending. These results are discussed in conjunction with current theories of depolarization—secretion coupling.

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Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ceccarelli B., Hurlbut W. P. Vesicle hypothesis of the release of quanta of acetylcholine. Physiol Rev. 1980 Apr;60(2):396–441. doi: 10.1152/physrev.1980.60.2.396. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Dodge F. A., Jr, Miledi R., Rahamimoff R. Strontium and quantal release of transmitter at the neuromuscular junction. J Physiol. 1969 Jan;200(1):267–283. doi: 10.1113/jphysiol.1969.sp008692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Dreyer F., Peper K. A monolayer preparation of innervated skeletal muscle fibres of the m. cutaneus pectoris of the frog. Pflugers Arch. 1974 Apr 22;348(3):257–262. doi: 10.1007/BF00587416. [DOI] [PubMed] [Google Scholar]
  7. Gaddum J. H. The action of adrenalin and ergotamine on the uterus of the rabbit. J Physiol. 1926 Mar 18;61(1):141–150. doi: 10.1113/jphysiol.1926.sp002280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gage P. W., Eisenberg R. S. Action potentials without contraction in frog skeletal muscle fibers with disrupted transverse tubules. Science. 1967 Dec 29;158(3809):1702–1703. doi: 10.1126/science.158.3809.1702. [DOI] [PubMed] [Google Scholar]
  9. Hagiwara S., Fukuda J., Eaton D. C. Membrane currents carried by Ca, Sr, and Ba in barnacle muscle fiber during voltage clamp. J Gen Physiol. 1974 May;63(5):564–578. doi: 10.1085/jgp.63.5.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Hubbard J. I. Microphysiology of vertebrate neuromuscular transmission. Physiol Rev. 1973 Jul;53(3):674–723. doi: 10.1152/physrev.1973.53.3.674. [DOI] [PubMed] [Google Scholar]
  12. JENKINSON D. H. The nature of the antagonism between calcium and magnesium ions at the neuromuscular junction. J Physiol. 1957 Oct 30;138(3):434–444. doi: 10.1113/jphysiol.1957.sp005860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Katz B., Miledi R. The timing of calcium action during neuromuscular transmission. J Physiol. 1967 Apr;189(3):535–544. doi: 10.1113/jphysiol.1967.sp008183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kharasch E. D., Mellow A. M., Silinsky E. M. Intracellular magnesium does not antagonize calcium-dependent acetylcholine secretion. J Physiol. 1981 May;314:255–263. doi: 10.1113/jphysiol.1981.sp013705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kita H., Van Der Kloot W. Effects of the ionophore X-537A on acetylcholine release at the frog neuromuscular junction. J Physiol. 1976 Jul;259(1):177–198. doi: 10.1113/jphysiol.1976.sp011460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. McLachlan E. M., Martin A. R. Non-linear summation of end-plate potentials in the frog and mouse. J Physiol. 1981 Feb;311:307–324. doi: 10.1113/jphysiol.1981.sp013586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McLaughlin A., Grathwohl C., McLaughlin S. The adsorption of divalent cations to phosphatidylcholine bilayer membranes. Biochim Biophys Acta. 1978 Nov 16;513(3):338–357. doi: 10.1016/0005-2736(78)90203-1. [DOI] [PubMed] [Google Scholar]
  19. Meiri U., Rahamimoff R. Activation of transmitter release by strontium and calcium ions at the neuromuscular junction. J Physiol. 1971 Jul;215(3):709–726. doi: 10.1113/jphysiol.1971.sp009493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mellow A. M. Equivalence of Ca2+ and Sr2+ in transmitter release from K+-depolarised nerve terminals. Nature. 1979 Nov 1;282(5734):84–85. doi: 10.1038/282084a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Miyamoto M. D. Binomial analysis of quantal transmitter release at glycerol treated frog neuromuscular junctions. J Physiol. 1975 Aug;250(1):121–142. doi: 10.1113/jphysiol.1975.sp011045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pagano R. E., Weinstein J. N. Interactions of liposomes with mammalian cells. Annu Rev Biophys Bioeng. 1978;7:435–468. doi: 10.1146/annurev.bb.07.060178.002251. [DOI] [PubMed] [Google Scholar]
  24. Papahadjopoulos D. Phospholipid model membranes. 3. Antagonistic effects of Ca2+ and local anesthetics on the permeability of phosphatidylserine vesicles. Biochim Biophys Acta. 1970 Sep 15;211(3):467–477. doi: 10.1016/0005-2736(70)90252-x. [DOI] [PubMed] [Google Scholar]
  25. Rahamimoff R., Meiri H., Erulkar S. D., Barenholz Y. Changes in transmitter release induced by ion-containing liposomes. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5214–5216. doi: 10.1073/pnas.75.10.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Silinsky E. M. An estimate of the equilibrium dissociation constant for calcium as an antagonist of evoked acetylcholine release: implications for excitation-secretion coupling. Br J Pharmacol. 1977 Dec;61(4):691–693. doi: 10.1111/j.1476-5381.1977.tb07562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Silinsky E. M. Enhancement by an antagonist of transmitter release from frog motor nerve terminals. Br J Pharmacol. 1978 Jul;63(3):485–493. doi: 10.1111/j.1476-5381.1978.tb07802.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Silinsky E. M. On the calcium receptor that mediates depolarization-secretion coupling at cholinergic motor nerve terminals. Br J Pharmacol. 1981 Jun;73(2):413–429. doi: 10.1111/j.1476-5381.1981.tb10438.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Stevens C. F. A comment on Martin's relation. Biophys J. 1976 Aug;16(8):891–895. doi: 10.1016/S0006-3495(76)85739-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zengel J. E., Magleby K. L. Changes in miniature endplate potential frequency during repetitive nerve stimulation in the presence of Ca2+, Ba2+, and Sr2+ at the frog neuromuscular junction. J Gen Physiol. 1981 May;77(5):503–529. doi: 10.1085/jgp.77.5.503. [DOI] [PMC free article] [PubMed] [Google Scholar]

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