Molecular and Chemical Neuropathology

, Volume 33, Issue 3, pp 163–174 | Cite as

The effect of glutamate and inhibitors of NMDA receptors on postdenervation decrease of membrane potential in rat diaphragm

  • A. Kh. Urazaev
  • N. V. Naumenko
  • G. I. Poletayev
  • E. E. Nikolsky
  • F. Vyskočil
Original Articles


The early postdenervation depolarization of rat diaphragm muscle fibers (8–10 mV within 3 h in vitro) is substantially smaller (3 mV) when muscles are bathed with 1×10−3 M l-glutamate (Glu) or 1×10−3 M N-methyl-d-aspartate (NMDA). The effects of Glu and NMDA are inhibited in a dose-dependent manner by competitive inhibitor 2-amino-5-phosphonovaleric acid (APV) withK i 6.3×10−4 M, by 2×10−7 M MK-801, which acts as an open channel inhibitor, by 2–3×10−4 Zn2+, which reacts with surface-located sites of the NMDA subtype of the glutamate receptor, and also by glycine-free solutions and 7-Cl-kynurenic acid, which inhibits the glycine binding sites on NMDA receptors. It follows that the effect of glutamate on early postdenervation depolarization is mediated by the NMDA subtype of glutamate receptor with similar pharmacological properties to those found in neurons. The only exception found was the glutamate-like action of 1×10−7 M MK-801, which partially prevented the early postdenervation depolarization when present in the muscle bath during the first 3 h after nerve section.

Index Entries

Glutamate NMDA receptor APV MK-801 Zn2+ neuromuscular junction NO denervation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amador M. and Dani J. A. (1991) MK-801 inhibition of nicotinic acetylcholine receptor channels.Synapse 7, 207–215.PubMedCrossRefGoogle Scholar
  2. Assaf S. Y. and Chung S.-H. (1984) Release of endogenous Zn2+ from brain tissue during activity.Nature 308, 734–736.PubMedCrossRefGoogle Scholar
  3. Berger U. V., Carter R. E., and Coyle J. T. (1995) The immunocytochemical localization ofN-acetylaspartyl glutamate, its hydrolysing enzyme NAALADase, and the NMDAR-1 receptor at a vertebrate neuromuscular junction.Neuroscience 64, 847–850.PubMedCrossRefGoogle Scholar
  4. Bray J. J., Hawken M. J., Hubbard J. I., Pockett S., and Wilson L. (1976) The membrane potential of rat diaphragm muscle fibers and the effect of denervation.J. Physiol. 255, 651–667.PubMedGoogle Scholar
  5. Davies J. and Watkins J. C. (1982) Actions of D and L form of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord.Brain Res. 235, 378–386.PubMedCrossRefGoogle Scholar
  6. Gu Y. and Huang L.-Y. M. (1994) Modulation of glycine affinity for NMDA receptors by extracellular Ca2+ in trigeminal neurones.J. Neurosci. 14, 4561–4570.PubMedGoogle Scholar
  7. Hahn J. S., Aizenmann E., and Lipton S. A. (1988) Central mammalian neurons normally resistant to glutamate toxicity are made sensitive by elevated extracellular Ca2+: toxicity is blocked by theN-methyl-d-aspartate antagonist MK-801.Proc. Natl. Acad. Sci. USA 85, 6556–6560.PubMedCrossRefGoogle Scholar
  8. Howell G. A., Welch M. G., and Frederickson C. J. (1984) Stimulation-induced uptake and release of zinc in hippocampal slices.Nature 308, 736–738.PubMedCrossRefGoogle Scholar
  9. Jahr C. E. and Stevens C. F. (1990) Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics.J. Neurosci. 10, 3178–3182.PubMedGoogle Scholar
  10. Johnson J. W. and Ascher P. (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons.Nature 325, 529–531.PubMedCrossRefGoogle Scholar
  11. Kemp J. A., Foster A. C., Leeson P. D., Priestly T., Tridgett R., Iversen L. L., et al. (1988) 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of theN-methyl-d-aspartate receptor complex.Proc. Natl. Acad. Sci. USA 85, 6547–6550.PubMedCrossRefGoogle Scholar
  12. Kerkut G. A., Shapiro A. and Walker R. J. (1967) The transport of14C-labelled material from CNS to muscle along a nerve trunk.Comp. Biochem. Physiol. 23, 729–748.PubMedCrossRefGoogle Scholar
  13. Klecker N. W. and Dingledine R. (1988) Requirement for glycine in activation of NMDA-receptors expressed inXenopus oocytes.Science 241, 835–837.CrossRefGoogle Scholar
  14. Legendre P. and Westbrook G. L. (1990) The inhibition of singleN-methyl-D-aspartate-activated channels by zinc ions on cultured rat neurones.J. Physiol. 429, 429–449.PubMedGoogle Scholar
  15. Masters B. A., Quaife C. J., Erickson J. C., Kelly E. J., Froelick G. L.. Zambrowicz B. P., et al. (1994) Metallothionein III is expressed in neurones that sequester zinc in synaptic vesicles.J. Neurosci. 14, 5844–5857.PubMedGoogle Scholar
  16. Mayer M. L., Westbrook G. L., and Vyklicky J. L. (1988) Sites of antagonist action onN-methyl-d-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique.J. Neurophysiol. 60, 645–663.PubMedGoogle Scholar
  17. Mayer M. L., Vyklicky L. J., and Westbrook G. L. (1989) Modulation of excitatory amino acid receptors by group II B metal cations in cultured mouse hippocampal neuronesJ. Physiol. 415, 329–350.PubMedGoogle Scholar
  18. Meister B., Arvidsson U., Zhang X., Jacobsson G., Villar M. J., and Hokfelt T. (1993) Glutamate transporter mRNA and glutamate-like immunoreactivity in spinal motoneurones.NeuroReport 5, 337–340.PubMedCrossRefGoogle Scholar
  19. Peters S., Koh J., and Choi D. W. (1987) Zinc selectively blocks the action ofN-methyl-d-aspartate on cortical neurones.Science 236, 589–593.PubMedCrossRefGoogle Scholar
  20. Schneggenburger R., Zhou Z., Konnerth A., and Neher E. (1993) Fractional contribution of calcium to the cation current through the glutamate receptor channels.Neuron 11, 133–143.PubMedCrossRefGoogle Scholar
  21. Stankovičová T., Zemková H., Breier A., Amler E., Burkhard M., and Vyskočil F. (1995) The effect of calcium and calcium channel blockers on sodium pump.Pfluegers Arch.-Eur. J. Physiol. 429, 716–721.CrossRefGoogle Scholar
  22. Urazaev A. Kh., Surovtsev V. A., Chikin A. V., Volkov E. M., Poletaev G. I., and Khamitov Kh. S. (1987) Neurotrophic control of the transmembrane Cl-pump in mammalian muscle fibers.Neurophysiology 19, 766–779 (in Russian).PubMedGoogle Scholar
  23. Urazaev A. Kh., Magsumov S. T., Poletaev G. I., Nikolsky E. E. and Vyskočil F. (1995) Muscle NMDA receptors regulate the resting membrane potential through NO-synthase.Physiol. Res. 44, 205–208.PubMedGoogle Scholar
  24. Urazaev A. Kh., Naumenko N. V., Poletaev G. I., Nikolsky E. E., and Vyskočil F. (1996a) Properties of NMDA-receptors in muscle fibre membrane. Abstract 8th International Congress of the Czech and Slovak Neurochemical Society, Martin, Slovakia, September 4–7, p. 83.Google Scholar
  25. Urazaev A. Kh., Naumenko N. V., Poletaev G. I., Nikolsky E. E., and Vyskočil, F. (1996b) Nitroprusside decreases the early postdenervation depolarization of diaphragm muscle fibres of the rat.Eur. J. Pharmacol. 316, 219–222.PubMedCrossRefGoogle Scholar
  26. Urazaev A. Kh., Naumenko N. V., Poletaev G. I., Nikolsky E. E., and Vyskočil F. (1997) Acetylcholine and carbachol prevent muscle depolarization in denervated rat diaphragm.NeuroReport 8, 403–406.PubMedCrossRefGoogle Scholar
  27. Waerhaug O. and Ottersen O. P. (1993) Demonstration of glutamate-like immunoreactivity at rat neuromuscular junctions by quantitative electron microscopic immunocytochemistry.Anat. Embryol. (Berl.) 188, 501–513.CrossRefGoogle Scholar
  28. Westbrook G. L. and Mayer M. L. (1987) Micromolar concentration of Zn2+ antagonize NMDA and GABA responses of hippocampal neurones.Nature 328, 640–643.PubMedCrossRefGoogle Scholar
  29. Wong E. H. F., Kemp J. A., Priestly T., Knight A. R., Woodruff G. N. and Iversen L. L. (1986) The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.Proc. Natl. Acad. Sci. USA 83, 7104–7108.PubMedCrossRefGoogle Scholar
  30. Wood E. R., Bussey T. J. and Philips A. G. (1994) A glycine antagonist 7-chlorkynurenic acid attenuates ischemia-induced learning deficits.NeuroReport 4, 151–154.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1998

Authors and Affiliations

  • A. Kh. Urazaev
    • 1
  • N. V. Naumenko
    • 1
  • G. I. Poletayev
    • 1
  • E. E. Nikolsky
    • 1
  • F. Vyskočil
    • 2
    • 3
  1. 1.Medical UniversityKazanRussia
  2. 2.Institute of PhysiologyAcademy of Sciences of the Czech RepublicPrague 4Czech Republic
  3. 3.Department of Animal Physiology and Developmental Biology, Faculty of SciencesCharles UniversityPragueCzech Republic

Personalised recommendations