Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones

Abstract

Excitatory amino acids act via receptor subtypes in the mammalian central nervous system (CNS)1–3. The receptor selectively activated by N-methyl-D-aspartic acid (NMDA) has been best characterized using voltage-clamp and single-channel recording; the results suggest that NMDA receptors gate channels that are permeable to Na+, K+ and other monovalent cations4–7. Various experiments suggest that Ca2+ flux is also associated with the activation of excitatory amino-acid receptors on vertebrate neurones8–11. Whether Ca2+ enters through voltage-dependent Ca2+ channels or through excitatory amino-acid-activated channels of one or more subtype is unclear. Mg2+ can be used to distinguish NMDA-receptor-activated channels from voltage-dependent Ca2+ channels, because at micromolar concentrations Mg2+ has little effect on voltage-dependent Ca2+ channels12 while it enters and blocks NMDA receptor channels4,5,7,13,14. Marked differences in the potency of other divalent cations acting as Ca2+ channel blockers compared with their action as NMDA antagonists also distinguish the NMDA channel from voltage-sensitive Ca2+ channels5,7. However, we now directly demonstrate that excitatory amino acids acting at NMDA receptors on spinal cord neurones increase the intracellular Ca2+ activity, measured using the indicator dye arsenazo III, and that this is the result of Ca2+ influx through NMDA receptor channels. Kainic acid (KA), which acts at another subtype of excitatory amino-acid receptor, was much less effective in triggering increases in intracellular free Ca2+.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Krogsgaard-Larsen, P., Honoré, T., Hansen, J. J., Curtis, D. R. & Lodge, D. Nature 284, 64–66 (1980).

    ADS  CAS  Article  Google Scholar 

  2. Watkins, J. C. & Evans, R. H. A. Rev. Pharmac. Tox. 21, 165–205 (1981).

    CAS  Article  Google Scholar 

  3. McLennan, H. Prog. Neurobiol. 20, 251–271 (1983).

    CAS  Article  Google Scholar 

  4. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. Nature 307, 462–465 (1984).

    ADS  CAS  Article  Google Scholar 

  5. Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. Nature 309, 261–263 (1984).

    ADS  CAS  Article  Google Scholar 

  6. Mayer, M. L. & Westbrook, G. L. J. Physiol., Lond. 354, 29–53 (1984).

    CAS  Article  Google Scholar 

  7. Mayer, M. L. & Westbrook, G. L. J. Physiol., Lond. 361, 65–90 (1985).

    CAS  Article  Google Scholar 

  8. Dingledine, R. J. Physiol., Lond. 343, 385–405 (1983).

    CAS  Article  Google Scholar 

  9. Bührle, C. P. & Sonnhof, U. Pflügers Arch. ges. Physiol. 396, 154–162 (1983).

    Article  Google Scholar 

  10. Zanotto, L. & Heinemann, U. Neurosci. Lett. 35, 79–84 (1983).

    CAS  Article  Google Scholar 

  11. Pumain, R. & Heinemann, U. J. Neurophysiol. 53, 1–16 (1985).

    CAS  Article  Google Scholar 

  12. Lansman, J. B., Hess, P. & Tsien, R. W. J. gen. Physiol. (in the press).

  13. Ault, B., Evans, R. H., Francis, A. S., Oakes, D. J. & Watkins, J. C. J. Physiol., Lond. 307, 413–428 (1980).

    CAS  Article  Google Scholar 

  14. Crunelli, V. & Mayer, M. L. Brain Res. 311, 392–396 (1984).

    CAS  Article  Google Scholar 

  15. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F., Pflügers Arch. ges. Physiol. 391, 85–100 (1981).

    CAS  Article  Google Scholar 

  16. Cull-Candy, S. G. & Ogden, D. C. Proc. R. Soc. B224, 367–373 (1985).

    ADS  CAS  Google Scholar 

  17. Hagiwara, S. & Bylerly, L. A. Rev. Neurosci. 4, 69–125 (1981).

    CAS  Article  Google Scholar 

  18. Smith, S. J., MacDermott, A. B. & Weight, F. F. Nature 304, 350–352 (1983).

    ADS  CAS  Article  Google Scholar 

  19. Gorman, A. L. F. & Thomas, M. V. J. Physiol., Lond. 308, 259–285 (1980).

    CAS  Article  Google Scholar 

  20. Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).

    ADS  CAS  Article  Google Scholar 

  21. Sladeczek, F., Pin, J. P., Récasens, M., Bockaert, J. & Weiss, S. Nature 317, 717–719 (1985).

    ADS  CAS  Article  Google Scholar 

  22. Schoffelmeer, A. M. N. & Mulder, A. H. J. Neurochem. 40, 615–621 (1983).

    CAS  Article  Google Scholar 

  23. Evans, R. H. & Watkins, J. C. J. Physiol., Lond. 277, 57P (1977).

    Google Scholar 

  24. Nowak, L. M. & Ascher, P. Soc. Neurosci. Abstr. 10, 23 (1984).

    Google Scholar 

  25. Mayer, M. L. & Westbrook, G. L. Soc. Neurosci. Abstr. 11, 785 (1985).

    Google Scholar 

  26. Ascher, P. & Nowak, L. J. Physiol., Lond. Proc. (in the press).

  27. Fabiato, A. & Fabiato, F. Ann. N.Y. Acad. Sci. 307, 491–522 (1978).

    ADS  CAS  Article  Google Scholar 

  28. Nowak, L. M. & Ascher, P. Soc. Neurosci. Abstr. 11, 953 (1985).

    Google Scholar 

  29. Lynch, G., Larson, J., Kelso, S., Barrinuevo, G. & Schottler, F. Nature 305, 719–721 (1983).

    ADS  CAS  Article  Google Scholar 

  30. Collingridge, G. L., Kehl, S. J. & McLennan, H. J. Physiol., Lond. 334, 33–46 (1983).

    CAS  Article  Google Scholar 

  31. Parsons, R. L. in Calcium in Drug Action (ed. Weiss, G. B.) 289–314 (Plenum, New York, 1978).

    Book  Google Scholar 

  32. Miledi, R. Proc. R. Soc. B209, 447–452 (1980).

    ADS  CAS  Google Scholar 

  33. Adams, D. J., Dwyer, T. M. & Hille, B. J. gen. Physiol. 75, 493–510 (1980).

    CAS  Article  Google Scholar 

  34. Edwards, C. Neuroscience 7, 1335–1366 (1982).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

MacDermott, A., Mayer, M., Westbrook, G. et al. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 321, 519–522 (1986). https://doi.org/10.1038/321519a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/321519a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing