A Possible Involvement of the Na-Ca Exchanger in Regulation of Transmitter Release at the Frog Neuromuscular Junction

  • Halina Meiri
  • Julian Zelingher
  • Rami Rahamimoff
Part of the Topics in the Neurosciences book series (TNSC, volume 1)


While the Important role of calcium ions in transmitter release has been well recognized (del Castillo & Stark, 1952; del Castillo & Katz, 1954; Jenkinson, 1957; Dodge & Rahamimoff, 1967; Katz & Miledi, 1969; Miledi, 1973), the involvement of sodium ions in regulation of the release process — although evident since 1952 (Fatt & Katz, 1952) — is still not completely understood. Sodium ions, although cannot replace calcium in the release process itself, can modulate the number of released transmitter quanta by controlling the metabolism of calcium in the nerve terminal (Kelly, 1965; Birks & Cohen, 1968; Colomo & Rahamimoff, 1968; Lev Tov & Rahamimoff, 1980). Both the influx of calcium ions into the depolarized neuronal axon and their extrusion from the axoplasm, are affected by extracellular sodium.


Nerve Terminal Transmitter Release Spontaneous Release Mepp Amplitude Extracellular Sodium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alvarez-Leefmans F.J., Rink T.J. and Tsien R.J. (1981). Free calcium ions in neurones of Helix aspersa measured with ion selective electrodes. J. Physiol. 315, 531–548.PubMedGoogle Scholar
  2. 2.
    Baker P.F. (1972). Transport of metabolism of calcium ions in nerve. Prog. Biophys. Molec. Biol. 24, 177–223.CrossRefGoogle Scholar
  3. 3.
    Baker P.F. and McNaughton P.S. (1976). Kinetics and energetics of calcium efflux from squid axons. J. Physiol. 276, 127–150.Google Scholar
  4. 4.
    Birks R.I., Burstyn P.G.R. and Firth D.R. (1968). The form of sodium-calcium competition at the frog myoneural junction. J. Gen. Physiol. 52, 887–907.PubMedCrossRefGoogle Scholar
  5. 5.
    Birks R.I. and Cohen M.W. (1965). Effects of sodium pump inhibitors on myoneural transmission in the frog. Int. Symposium of Muscle. New York Academic Press.Google Scholar
  6. 6.
    Blaustein M.P. (1976). The ins and outs of calcium transport in squid axons: internal and external ion activation of calcium efflux. Fed. Proc. 35, 2574–2578.PubMedGoogle Scholar
  7. 7.
    Blaustein M.P. (1977). Effects of internal and external cations and of ATP on sodium-calcium and calcium-calcium exchange in squid axons. Biophys. J. 20, 79–111.PubMedCrossRefGoogle Scholar
  8. 8.
    Blaustein M.P. and Osborn C.Y. (1975). The infulence of sodium on calcium fluxes in pinched-off nerve terminals in vitro. J. Physiol. 247, 657–686.PubMedGoogle Scholar
  9. 9.
    Blaustein M.P., Russell J.M. and Dewer P. (1974). Calcium efflux from internally dialized squid axons. J. Supram. Struct. 2, 558–581.CrossRefGoogle Scholar
  10. 10.
    Blaustein M.P. and Wiesmann W.P. (1970). Effect of sodium ions on calcium movements in isolated synaptic terminals. Proc Natl. Acad. Sci. USA 66, 664–671.PubMedCrossRefGoogle Scholar
  11. 11.
    Brinley F.J., Jr., Spangler S.G. and Mullins L.J. (1975). Calcium and EDTA fluxes in dialyzed squid axons. J. Gen. Physiol. 66, 223–250.PubMedCrossRefGoogle Scholar
  12. 12.
    Colomo F. and Rahamimoff R. (1968). Interaction between sodium and calcium ions in the process of transmitter release at the neuromuscular junction. J. Physiol. 198, 203–218.PubMedGoogle Scholar
  13. 13.
    del Castillo R. and Katz B. (1954). The effect of magnesium on motor nerve endings. J. Physiol. 124, 553–559.Google Scholar
  14. 14.
    del Castillo R. and Stark L. (1952). The effect of calcium on motor nerve endplate potentials. J. Physiol. 116, 507–515.Google Scholar
  15. 15.
    DiPolo R. (1974). Effect of ATP on the calcium efflux in dialyzed squid giant axons. J. Gen. Physiol. 64, 503–517.PubMedCrossRefGoogle Scholar
  16. 16.
    DiPolo R. (1978). Ca pump driven by ATP in squid axons. Nature 274, 390–392.PubMedCrossRefGoogle Scholar
  17. 17.
    DiPolo R. (1979). Calcium influx in internally dialyzed squid giant axons. J. Gen. Physiol. 73, 91–113.PubMedCrossRefGoogle Scholar
  18. 18.
    DiPolo R. and Beauge L. (1979). Physiological role of ATP driven calcium pump in squid axon. Nature 278, 271–273.PubMedCrossRefGoogle Scholar
  19. 19.
    DiPolo R. and Beauge L. (1980). Mechanisms of calcium transport in the giant axon of the squid and their physiological role. Cell Calcium 1, 147–169.CrossRefGoogle Scholar
  20. 20.
    DiPolo R. and Beauge L. (1983). The calcium pump and sodium-calcium exchange in squid axons. Ann. Rev. Physiol. 45, 313–324.CrossRefGoogle Scholar
  21. 21.
    DiPolo R., Requena J., Brinley F.J., Mullins L.J. Scarpa A. and Tiffert T. (1976). Ionized calcium concentrations in squid axons. J. Gen. Physiol. 67, 433–467.PubMedCrossRefGoogle Scholar
  22. 22.
    DiPolo R., Rojas H. and Beauge L. (1982). Calcium entry at rest and during prolonged depolarization in dialyzed squid axons. Cell Calcium 3, 19–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Dodge F.A. and Rahamimoff R. (1967). Co-operative action of calcium ions in transmitter release at the neuromuscular junction. J. Physiol. 193, 419–432.PubMedGoogle Scholar
  24. 24.
    Fatt P. and Katz B. (1952). The effect of sodium ions on neuromuscular transmission. J. Physiol. 118, 73–87.PubMedGoogle Scholar
  25. 25.
    Frankenhauser B. (1959). Steady state inactivation of sodium permeability of myelinated nerve fibers of Xenopus Laevidis. J. Physiol. 148, 671–676.Google Scholar
  26. 26.
    Gage P.W. and Quastel D.M.J. (1966). Competition between sodium and calcium ions in transmitter release at mammalian neuromuscular junction. J. Physiol. 185, 95–123.PubMedGoogle Scholar
  27. 27.
    Hess R. and Weingart R. (1980). Intracellular free calcium modified by pHi in sheep cardiac Purkinje fibres. J. Physiol. 307, 60P-61P.Google Scholar
  28. 28.
    Hodgkin A.L. and Katz B. (1949). The effect of sodium ions on the electrical activity of the giant axon of the squid. J. Physiol. 108, 37–77.PubMedGoogle Scholar
  29. 29.
    Huxley A.F. and Stamfli R. (1951). Direct determination of membrane resting potential and action potential in single myelinated nerve fibers. J. Physiol. 112, 476–495.PubMedGoogle Scholar
  30. 30.
    Jenkinson D.H. (1957). The nature of the antagonism between calcium and magnesium ions at the neuromuscular junction. J. Physiol. 138, 434–444.PubMedGoogle Scholar
  31. 31.
    Katz B. and Miledi R. (1965). The effect of calcium on acetylcholine release from motor nerve terminals. Proc. R. Soc. 161, 495–503.Google Scholar
  32. 32.
    Katz B. and Miledi R. (1968). The role of calcium in neuromuscular facilitation. J. Physiol. 195, 481–492.PubMedGoogle Scholar
  33. 33.
    Katz B. and Miledi R. (1969). Tetrodotoxin resistant electrical activity in presynaptic terminals. J. Physiol. 203, 459–487.PubMedGoogle Scholar
  34. 34.
    Kelly Y.S. (1965). Ca2+ at the neuromuscular junction. Nature 205, 296–297.PubMedCrossRefGoogle Scholar
  35. 35.
    Lea T.Y. and Ashley C.C. (1978). Increase in free calcium in muscle after exposure to CO2. Nature 275, 236–238.PubMedCrossRefGoogle Scholar
  36. 36.
    Lev-Tov A. and Rahamimoff R. (1980). A study of tetanic and post-tetanic potentiation of miniature endplate potentials at the neuromuscular junction. J. Physiol. 309, 247–273.PubMedGoogle Scholar
  37. 37.
    Meiri H. and Rahamimoff R. (1972). Fluctuation in endplate potential amplitude and calcium ions. Isr. J. Med. Sci. 8, 4.Google Scholar
  38. 38.
    Miledi R. (1973). Transmitter release induced by injection of calcium ions into nerve terminals. Proc. R. Soc. B. 183, 421–425.CrossRefGoogle Scholar
  39. 39.
    Moody W.J. (1981). The ionic mechanism of intracellular pH regulation in crayfish neurones. J. Physiol. 316, 293–308.PubMedGoogle Scholar
  40. 40.
    Moody W.J. (1984). Effects of intracellular H+ on the electrical properties of excitable cells. Ann. Rev. Neurosci. 7, 257–278.PubMedCrossRefGoogle Scholar
  41. 41.
    Mullins L.J. (1977). A mechanism for Na/Ca transport. J. Gen. Physiol. 70, 681–695.PubMedCrossRefGoogle Scholar
  42. 42.
    Mullins L.J. (1979). The generation of electric currents in cardiac fibers by Na/Ca exchange. Am. J. Physiol. 236, C103–C110.PubMedGoogle Scholar
  43. 43.
    Mullins L.J. and Brinley F.J., Jr. (1975). Sensitivity of calcium efflux from squid axons to changes in membrane potentials. J. Gen. Physiol. 65, 135–152.PubMedCrossRefGoogle Scholar
  44. 44.
    Rahamimoff R. (1968). A dual effect of calcium ions on neuromuscular facilitation. J. Physiol. 195, 471–480.PubMedGoogle Scholar
  45. 45.
    Rahsmimoff H., Papazlan D., Stanley M., Goldin, Spanler R. and Abramovitz E. (1980). Synaptosome-derived Ca transport systems: Properties and Purification, 28th Int. Adv. Physiol. Soc. Vol. 36, Cellular Analogues of Conditioning and Neural Plasticity. 0. Feher, F. Yoo (Eds.)Google Scholar
  46. 46.
    Rahamimoff M. and Spanier R. (1979). Sodium dependent calcium uptake in membrane vesicles derived from rat brain synaptosomes. FEBS Lett. 104, 111–114.PubMedCrossRefGoogle Scholar
  47. 47.
    Rahamimoff R. and Yaari Y. (1973). Delayed release of transmitter at the frog neuromuscular junction. J. Physiol. 228, 241–257.PubMedGoogle Scholar
  48. 48.
    Requena J., DiPolo R., Brinley F.J., Jr., and Mullins L.J. (1977). The control of ionized calcium in squid axons. J. Gen. Physiol. 70, 329–353.PubMedCrossRefGoogle Scholar
  49. 49.
    Reuter H. and Seitz N. (1968). Dependence of calcium influx from cardiac muscle on temperature and external ion composition. J. Physiol. 195, 451–470.PubMedGoogle Scholar
  50. 50.
    Rink T.J., Tsien R.Y and Marner A.E. (1980). Free calcium in Xenopus embryos measured with ion selective microelectrodes. Nature 253, 258–260.Google Scholar
  51. 51.
    Smith S.J. and Zucker R.S. (1980). Aequorin response facilitation and intracellular calciUM accumulation in molluscan neurones. J. Physiol. 300, 167–196.PubMedGoogle Scholar
  52. 52.
    Sulakhe P.V. and Louis P.Y.S.T. (1980). Passive and active calcium fluxes across plasma membranes. Prog. Blephys. Melec. Biol. 35, 135–195.CrossRefGoogle Scholar
  53. 53.
    Takeuchi A. and Takeuchl N. (1960). On the permeability of endplate membrane during the action of transmitter. J. Physiol. 154, 52–67.PubMedGoogle Scholar
  54. 54.
    Themas R.C. (1972). lntracellular sodium activity and the sodium pump in snail neurons. J. Physiol. 220, 59–71.Google Scholar
  55. 55.
    Taten R.Y., Pezzan T. and Rink T.J. (1982). Calclum homeostasis in Intact lymphocytes: Cytoplasmic free calcium monitored with a now Intracel lularly trapped fluorescent Indicator. J. Cell. Biol. 94, 325–334.CrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1986

Authors and Affiliations

  • Halina Meiri
    • 1
  • Julian Zelingher
    • 1
  • Rami Rahamimoff
    • 1
  1. 1.Department of PhysiologyHebrew University-Hadassah Medical SchoolJerusalemIsrael

Personalised recommendations