The Effects of Glutamate on Spontaneous Acetylcholine Secretion Processes in the Rat Neuromuscular Synapse

  • 23 Accesses

  • 4 Citations


Experiments on rat diaphragm muscles showed that glutamate (10 μM – 1 mM) had no effect on the mean frequency, interspike intervals, and amplitude-time characteristics of miniature endplate potentials, but had a suppressive action on non-quantum secretion (the intensity of which was assessed in terms of the H effect). The effect of glutamate was markedly concentration-dependent and was completely overcome by blockade of NMDA receptors, inhibition of NO synthase, and by binding of NO molecules in the extracellular space by hemoglobin. It is suggested that glutamate can modulate the non-quantum release of acetylcholine, initiating the synthesis of NO molecules in muscle fibers via activation of NMDA receptors followed by the retrograde action of NO on nerve terminals.

This is a preview of subscription content, log in to check access.


  1. 1.

    I. P. Ashmarin and P. V. Stukalov, Neurochemistry [in Russian], IBKh, Russian Academy of Medical Sciences, Moscow (1996).

  2. 2.

    M. R. Mukhtarov, A. Kh. Urazaev, E. E. Nikol'skii, and F. Vyskochil, “Modulation of the intensity of non-quantum neurotransmitter secretion in the neuromuscular junction of the rat by nitric oxide (NO),” Ros. Fiziol. Zh. im. I. M. Sechenova, 86, No. 3, 335–342 (2000).

  3. 3.

    A. Kh. Urazaev and A. L. Zefirov, “The physiological role of nitric oxide,” Usp. Fiziol. Nauk, 30, No. 1, 54–72 (1999).

  4. 4.

    A. Kh. Urazaev, S. T. Magsumov, and G. I. Poletaev, “L-glutamate-a contender for the role of a neural factor controlling the membrane potential of mammalian muscle fibers,” Ros. Fiziol. Zh. im. I. M. Sechenova, 82, No. 1, 85–89 (1996).

  5. 5.

    U. V. Berger, R. E. Carter, and J. T. Coyle, “The immunocytochemical localization of N-acetylaspartyl glutamate, its hydrolysing enzyme NAALADase, and the NMDAR-1 receptor at a vertebrate neuromuscular junction,” Neurosci., 64, No. 4, 847–850 (1995).

  6. 6.

    J. T. Coyle, “The nagging question of the function of N-acetylaspartylglutamate,” Neurobiology of Disease, 4, 231–238 (1997).

  7. 7.

    V. Dolezal and F. Tucek, “The synthesis and release of acetylcholine in normal and denervated rat diaphragms during incubation in vitro,” J. Physiol., 334, 461–474 (1983).

  8. 8.

    I. R. Duce, in: Comparative Invertebrate Neurochemistry, G. G. Lunt and R. W. Olsen (eds.), Cornell University Press, Ithaca, New York (1988), pp. 42–89.

  9. 9.

    W. M. Fu, H. C. Liou, Y. H. Chen, and S. M. Wang, “Coexistence of glutamate and acetylcholine in the developing motoneurons,” Chin. J. Physiol., 41, No. 3, 127–132 (1998).

  10. 10.

    W. M. Fu, J. C. Liou, Y. H. Lee, and H. C. Liou, “Potentiation of neurotransmitter release by activation of presynaptic glutamate receptors at developing neuromuscular synapses of Xenopus,” J. Physiol. (London), 489, No. 3, 813–823 (1995).

  11. 11.

    W. M. Fu and J. J. Liu, “Regulation of acetylcholine release by presynaptic nicotinic receptors at developing neuromuscular synapses,” Mol. Pharmacol., 51, No. 3, 390–398 (1997).

  12. 12.

    Z. Grozdanovic and R. Gossrau, “Co-localization of nitric oxide synthase I (NOS I) and NMDA receptor subunit I (NMDAR-1) at the neuromuscular junction in rat and mouse skeletal muscle,” Cell Tiss. Res., 291, 57–63 (1998).

  13. 13.

    M. Israel, B. Lesbats, and J. Bruner, “Glutamate and acetylcholine release from cholinergic nerve terminals. Calcium control of the specificity of the release mechanism,” Neurochem. Int, 22,. 53–58 (1993).

  14. 14.

    B. Katz and R. Miledi, “Transmitter leakage from motor nerve endings,” Proc. Roy. Soc. London Ser., 196, 59–72 (1977).

  15. 15.

    H. C. Liou, R. S. Yang, and W. M. Fu, “Potentiation of spontaneous acetylcholine release from motor nerve terminals by glutamate in Xenopus tadpoles,” Neurosci., 75, No. 1, 325–331 (1996).

  16. 16.

    B. Meister, U. Arvidsson, X. Zhang, G. Jacobsson, M. J. Villar, and T. Hokfeld, “Glutamate transporter mRNA and glutamate-like immunoreactivity in spinal motoneurones,” NeuroReport, 5, No. 3, 337–340 (1993).

  17. 17.

    J. F. Mitchell and A. Silver, “The spontaneous release of acetylcholine from the denervated hemidiaphragms of the rat,” J. Physiol., 66, 657–669 (1963).

  18. 18.

    L. Oliver, O. Goureau, Y. Courtois, and M. Vigny, “Accumulation of NO-synthase (type 1) at the neuromuscular junction in adult mice,” NeuroReport, 7, 924–926 (196).

  19. 19.

    E. M. Schuman and D. V. Madison, “Nitric oxide and synaptic function,” Ann. Rev. Neurosci., 17, 114–119 (1996).

  20. 20.

    B. S. Slusher M. B. Robinson, G. Tsai, M. L. Simmons, S. S. Richards, and J. T. Coyle, “Rat brain N-acetylated alpha-lined acidic dipeptidase activity. Purification and immunologic characterization,” J. Biol. Chem., 265, No. 21, 297–301 (1999).

  21. 21.

    Y.-A. Sun and M.-M. Poo, “Non-quantal release of acetylcholine at a developing neuromuscular synapse in culture,” J. Neurosci., 5, No. 3, 634–642 (1985).

  22. 22.

    S. Thesleff, “Functional aspects of quantal and non-quantal release of acetylcholine at the neuromuscular junction,” Progr. Brain Res., 84, 93–99 (1990).

  23. 23.

    G. Tsai, B. L. Stauch, J. J. Vornov, J. K. Deshpande, and J. T. Coyle, “Selective release of N-acetylaspartylglutamate from rat optic nerve terminals in vitro,” Brain Res., 518, 313–316 (1990).

  24. 24.

    A. Kh. Urazaev, “Nitric oxide is the retrograde messenger providing the neurotrophic control of membrane potential in muscle fibers of rats,” Neirokhimiya, 12, No. 2, 75–76 (1995).

  25. 25.

    A. Kh. Urazaev, S. T. Magsumov, G. I. Poletaev, E. E. Nikolsky, and F. Vyskocil, “Muscle NMDA receptors regulate the resting membrane potential through NO-synthase,” Physiol. Res., 44, 205–208 (1995).

  26. 26.

    A. Kh. Urazaev, N. V. Naumenko, G. I. Poletaev, E. E. Nikolsky, and F. Vyskocil, “Acetylcholine and carbachol prevent muscle depolarization in denervated rat diaphragm,” NeuroReport, 8, No. 2, 403–406 (1997).

  27. 27.

    A. Kh. Urazaev, N. V. Naumenko, G. I. Poletaev, E. E. Nikolsky, and F. Vyskocil, “The effect of glutamate and inhibitors of NMDA receptors on postdenervation decrease of membrane potential in rat diaphragm,” Mol. Chem. Neuropathol., 33, No. 3, 163–174 (1998).

  28. 28.

    S. Vyas and H. F. Bradford, “Co-release of acetylcholine, glutamate and taurine from synaptosomes of Torpedo electric organ,” Neurosci. Lett., 82, 58–64 (1987).

  29. 29.

    F. Vyskocil and P. Illes, “Non-quantal release of acetylcholine affects polyneuronal innervation on developing rat muscle fibers,” Eur. J. Neurosci., 5, 1677–1683 (1993).

  30. 30.

    F. Vyskocil and P. Illes, “Non-quantal release of transmitter at mouse neuromuscular junction and its dependence on the activity of Na+, K+-ATPase,” Pflügers Arch., 370, 295–297 (1997).

  31. 31.

    O. Waerhaug and O. P. Ottersen, “Demonstration of glutamate-like immunoreactivity at rat neuromuscular junctions by quantitative electron microscopic immunocytochemistry,” Anat. Embryol. (Berlin), 188, No. 5, 501–513 (1993).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Malomuzh, A.I., Mukhtarov, M.R., Urazaev, A.K. et al. The Effects of Glutamate on Spontaneous Acetylcholine Secretion Processes in the Rat Neuromuscular Synapse. Neurosci Behav Physiol 32, 577–582 (2002).

Download citation

  • glutamate
  • neuromuscular synapse
  • quantum secretion
  • non-quantum secretion
  • acetylcholine
  • nitric oxide