Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones (original) (raw)

Nature volume 309, pages 261–263 (1984)Cite this article

Abstract

Acidic amino acids are putative excitatory synaptic transmitters1,2, the ionic mechanism of which is not well understood. Recent studies with selective agonists and antagonists suggest that neurones of the mammalian central nervous system possess several different receptors for acidic amino acids3,4, which in turn are coupled to separate conductance mechanisms5. _N_-methyl-D-aspartic acid (NMDA) is a selective agonist for one of these receptors3,4. The excitatory action of amino acids acting at NMDA receptors is remarkably sensitive to the membrane potential and it has been suggested that the NMDA receptor is coupled to a voltage-sensitive conductance6–9. Recently, patch-clamp experiments have shown the voltage-dependent block by Mg2+ of current flow through ion channels activated by L-glutamate10. We now show using voltage-clamp experiments on mouse spinal cord neurones that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+ from the extracellular fluid. This provides further evidence that Mg2+ blocks inward current flow through ion channels linked to NMDA receptors.

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References

  1. Watkins, J. C. & Evans, R. H. A. Rev. Pharmac. Tox. 21, 165–204 (1981).
    Article CAS Google Scholar
  2. Johnson, J. L. Prog. Neurobiol. 10, 155–202 (1978).
    Article CAS Google Scholar
  3. Watkins, J. C. . in Amino Acid Neurotransmitters (eds DeFeudis, F. V. & Mandel, P.) 205–212 (Raven, New York, 1981).
    Google Scholar
  4. Watkins, J. C., Davies, J., Evans, R. H., Francis, A. A. & Jones, A. in Glutamate as a Neurotransmitter (eds DiChiara, G. & Gessa, G. L.) 263–273 (Raven, New York, 1981).
    Google Scholar
  5. MacDonald, J. F. & Porietis, A. V. Brain Res. 245, 175–178 (1982).
    Article CAS Google Scholar
  6. MacDonald, J. F. & Wojtowicz, J. M. Can. J. Physiol. Pharmac. 60, 282–296 (1982).
    Article CAS Google Scholar
  7. MacDonald, J. F., Porietis, A. V. & Wojtowicz, J. M. Brain. Res. 237, 248–253 (1982).
    Article CAS Google Scholar
  8. Dingledine, R. J. Physiol., Lond. 343, 385–405 (1983).
    Article CAS Google Scholar
  9. Flatman, J. A., Schwindt, P.C., Crill, W. E. & Stafstrom, C. E. Brain Res. 266, 169–173 (1983).
    Article CAS Google Scholar
  10. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. Nature 307, 492–465 (1984).
    Article ADS Google Scholar
  11. Ransom, B. R., Neale, E., Henkart, M., Bullock, P. N. & Nelson, P. G. J. Neurophysiol. 40, 1132–1150 (1977).
    Article CAS Google Scholar
  12. Guthrie, P. B. & Brenneman, D. E. Soc. Neurosci. Abstr. 8, 233 (1982).
    Google Scholar
  13. Mayer, M. L. & Westbrook, G. L. J. Physiol., Lond. 340, 19–45 (1983).
    Article CAS Google Scholar
  14. Khrishtal, O. A. Akad. Nauk. SSSR 231, 1003–1005 (1976).
    Google Scholar
  15. Engberg, I., Flatman, J. A. & Lambert, J. D. C. Br. J. Pharmac. 64, 384–385 P.
  16. Engberg, I., Flatman, J. A. & Lambert, J. D. C. J. Physiol., Lond. 288, 227–261 (1979).
    CAS PubMed Google Scholar
  17. Coronado, R. & Miller, C. Nature 280, 807–810 (1979).
    Article ADS CAS Google Scholar
  18. Neher, E. & Steinbach, J. H. J. Physiol., Lond. 277, 153–176 (1978).
    Article CAS Google Scholar
  19. Ogden, D. C., Siegelbaum, S. A. & Colquhoun, D. Nature 289, 596–598 (1981).
    Article ADS CAS Google Scholar

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Authors and Affiliations

  1. Department of Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK
    Mark L. Mayer
  2. Laboratory of Developmental Neurobiology, NICHD, Building 36, Room 2A21, National Institutes of Health, Bethesda, Maryland, 20205, USA
    Gary L. Westbrook & Peter B. Guthrie

Authors

  1. Mark L. Mayer
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  2. Gary L. Westbrook
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  3. Peter B. Guthrie
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Mayer, M., Westbrook, G. & Guthrie, P. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.Nature 309, 261–263 (1984). https://doi.org/10.1038/309261a0

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