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.

Glycine potentiates the NMDA response in cultured mouse brain neurons

Nature volume 325, pages 529–531 (1987)Cite this article

Abstract

Transmitters mediating 'fast' synaptic processes in the vertebrate central nervous system are commonly placed in two separate categories that are believed to exhibit no interaction at the receptor level. The 'inhibitory transmitters' (such as glycine and GABA) are considered to act only on receptors mediating a chloride conductance increase, whereas 'excitatory transmitters' (such as L-glutamate) are considered to activate receptors mediating a cationic conductance increase1. The best known excitatory receptor is that specifically activated by N-methyl-D-aspartate (NMDA)2 which has recently been characterized at the single channel level3–5. The response activated by NMDA agonists is unique in that it exhibits a voltage-dependent Mg block3,6. We report here that this response exhibits another remarkable property: it is dramatically potentiated by glycine. This potentiation is not mediated by the inhibitory strychnine-sensitive glycine receptor7,8, and is detected at a glycine concentration as low as 10 nM. The potentiation can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists. Thus, in addition to its role as an inhibitory transmitter, glycine may facilitate excitatory transmission in the brain through an allosteric9 activation of the NMDA receptor.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Iversen, L. L. Proc. R. Soc. B221, 245–260 (1984).

    ADS  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

  4. Cull-Candy, S. G. & Usowicz, M. M. Nature 325, 525–528 (1987).

    ADS  CAS  Article  Google Scholar 

  5. Jahr, C. E. & Stevens, C. F. Nature 325, 522–525 (1987).

    ADS  CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

  7. Curtis, D. R., Hösli, L. & Johnston, G. A. R. Exp. Brain Res. 6, 1–18 (1968).

    CAS  Article  Google Scholar 

  8. Graham, D., Pfeiffer, F., Simler, R. & Betz, H. Biochemistry 24, 990–994 (1985).

    CAS  Article  Google Scholar 

  9. Monod, J., Wyman, J. & Changeux, J. P. J. molec. Biol. 12, 88–118 (1965).

    CAS  Article  Google Scholar 

  10. Werman, R., Davidoff, R. A. & Aprison, M. H. Nature 214, 681–683 (1967).

    ADS  CAS  Article  Google Scholar 

  11. Hamill, O. P., Bormann, J. & Sakmann, B. Nature 305, 805–807 (1983).

    ADS  CAS  Article  Google Scholar 

  12. Kiskin, N. I., Krishtal, O. A. & Tsyndrenko, A. Ya. Neurosci. Lett. 63, 225–230 (1986).

    CAS  Article  Google Scholar 

  13. Ferraro, T. N. & Hare, T. A. Brain Res. 338, 53–60 (1985).

    CAS  Article  Google Scholar 

  14. Sigvardt, K. A., Grillner, S., Wallen, P. & Van Dongen, P. A. M. Brain Res. 336, 390–395 (1985).

    CAS  Article  Google Scholar 

  15. Herrling, P. L., Morris, R. & Salt, T. E. J. Physiol., Lond. 339, 207–222 (1983).

    CAS  Article  Google Scholar 

  16. Fagg, G. E. Trends Neurosci. 8, 207–210 (1985).

    CAS  Article  Google Scholar 

  17. Nakajima, Y. J. comp. Neurol. 156, 375–402 (1974).

    Article  Google Scholar 

  18. Choi, D. W., Farb, D. H. & Fischbach, G. D. Nature 269, 342–344 (1977).

    ADS  CAS  Article  Google Scholar 

  19. Study, R. E. & Barker, J. L. Proc. natn. Acad. Sci. U.S.A. 78, 7180–7184 (1981).

    ADS  CAS  Article  Google Scholar 

  20. Bormann, J. & Sakmann, B. IUPHAR 9th int. Congr. Pharmac. Abstr. S13–14 (Macmillan, London, 1984).

    Google Scholar 

  21. Haefely, W. E., Kyburz, E., Gerecke, M. & Möhler, H. Adv. Drug. Res. 14, 165–322 (1985).

    CAS  Google Scholar 

  22. Ransom, B. R., Neale, E., Henkart, M., Bullock, P. N. & Nelson, P. G. J. Neurophysiol. 40, 1132–1150 (1977).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  24. Yellen, G. Nature 296, 357–359 (1982).

    ADS  CAS  Article  Google Scholar 

  25. Johnson, J. & Ascher, P. Soc. Neurosci. Abstr. 12, 58 (1986).

    Google Scholar 

  26. Vyklicky, L. et al. Brain Res. 363, 148–151 (1986).

    CAS  Article  Google Scholar 

  27. Ascher, P., Nowak, L. & Kehoe, J. S. in Ion channels in Neural Membranes (eds Ritchie, J. M., Keynes, R. D. & Bolis, L.) 283–295 (Liss, New York, 1986).

    Google Scholar 

  28. Nelson, P. G., Ransom, B. R., Henkart, M. & Bullock, P. N. J. Neurophysiol. 40, 1178–1187 (1977).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Neurobiologie, Ecole Normale Supérieure, 46 rue d'Ulm, Paris, 75005, France

    J. W. Johnson & P. Ascher

Authors
  1. J. W. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Ascher
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Johnson, J., Ascher, P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325, 529–531 (1987). https://doi.org/10.1038/325529a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/325529a0

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

Advanced 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