Skip to main content
Log in

Flux coupling in a neuronal glutamate transporter

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

SYNAPTIC transmission is commonly terminated by diffusion and reuptake of neurotransmitter from the synaptic cleft. Glutamate reuptake prevents neurotoxicity and sets the lower limit for the concentration of extracellular glutamate, so it is important to understand the thermodynamics of this process. Here we use voltage clamping with a pH-sensitive fluorescent dye to monitor electrical currents and pH changes associated with flux of glutamate mediated by the human neuronal glutamate transporter EAAT3. In contrast to a previous model1, we find that three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell. This coupling can support a transmembrane glutamate concentration gradient ([Glu]in/[Glu]out) exceeding 106 under equilibrium conditions, and would allow the transporter to continue removing glutamate over a wide range of ionic conditions.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bouvier, M., Szatkowski, M., Amato, A. & Attwell, D. Nature 360, 471–474 (1992).

    Article  ADS  CAS  Google Scholar 

  2. Kanner, B. I. & Sharon, I. Biochemistry 17, 3949–3953 (1978).

    Article  CAS  Google Scholar 

  3. Barbour, B., Brew, H. & Attwell, D. Nature 335, 433–435 (1988).

    Article  ADS  CAS  Google Scholar 

  4. Erecinska, M., Wantorsky, D. & Wilson, D. F. J. Biol. Chem. 258, 9069–9077 (1983).

    CAS  PubMed  Google Scholar 

  5. Nelson, P. J., Dean, G. E., Aronson, P. S. & Rudnick, G. Biochemistry 22, 5459–5463 (1983).

    Article  CAS  Google Scholar 

  6. Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P. & Amara, S. G. Nature 375, 599–603 (1995).

    Article  ADS  CAS  Google Scholar 

  7. Wadiche, J. I., Amara, S. G. & Kavanaugh, M. P. Neuron 15, 721–728 (1995).

    Article  CAS  Google Scholar 

  8. Larsson, H. P., Picaud, S. A., Werblin, F. S. & Lecar, H. Biophys. J. 70, 733–742 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Eliasof, S. & Jahr, C. E. Proc. Natl Acad. Sci. USA 93, 4153–4158 (1996).

    Article  ADS  CAS  Google Scholar 

  10. Billups, B., Rossi, D. & Attwell, D. J. Neurosci. (in the press).

  11. Kanai, Y. & Hediger, M. A. Nature 360, 467–471 (1992).

    Article  ADS  CAS  Google Scholar 

  12. Arriza, J. L. et al. J. Neurosci. 14, 5559–5569 (1994).

    Article  CAS  Google Scholar 

  13. Billups, B. & Attwell, D. Nature 379, 171–174 (1996).

    Article  ADS  CAS  Google Scholar 

  14. Zerangue, N. & Kavanaugh, M. P. J. Physiol. (Lond.) 493, 419–423 (1996).

    Article  CAS  Google Scholar 

  15. Webb, D. J. & Nuccitelli, R. J. Cell Bioi. 91, 562–567 (1981).

    Article  CAS  Google Scholar 

  16. Burger, P. M. et al. Neuron 3, 715–720 (1989).

    Article  CAS  Google Scholar 

  17. Szatkowski, M., Barbour, B. & Attwell, D. Nature 348, 443–446 (1990).

    Article  ADS  CAS  Google Scholar 

  18. Hansen, A. J. Physiol. Rev. 65, 101–148 (1985).

    Article  CAS  Google Scholar 

  19. Szatkowski, M. & Attwell, D. Trends Neurosci. 17, 359–365 (1994).

    Article  CAS  Google Scholar 

  20. Benveniste, H., Drejer, J., Schousboe, A. & Diemer, N. H. J. Neurochem. 43, 1369–1374 (1984).

    Article  CAS  Google Scholar 

  21. Rothstein, J. D. et al. Neuron 16, 675–686 (1996).

    Article  CAS  Google Scholar 

  22. Chaudry, F. A. et al. Neuron 15, 711–720 (1995).

    Article  Google Scholar 

  23. Rothstein, J. D. et al. Neuron 13, 713–725 (1994).

    Article  CAS  Google Scholar 

  24. Saugstad, J. A., Segerson, T. P. & Westbrook, G. L. in Excitatory Amino Acids and Synaptic Transmission (eds Wheal, H. & Thomson, A.) 77–85 (Academic, London, 1995).

    Google Scholar 

  25. Trussel, L. O. & Fischbach, G. D. Neuron 3, 209–218 (1989).

    Article  Google Scholar 

  26. Patneau, D. K. & Mayer, M. L. J. Neurosci. 10, 2385–2399 (1990).

    Article  CAS  Google Scholar 

  27. Chan, P. H., Kerlan, R. & Fishman, R. A. J. Neurochem. 40, 309–316 (1983).

    Article  CAS  Google Scholar 

  28. Barbour, B., Szatkowski, M., Ingledew, N. & Attwell, D. Nature 342, 918–920 (1989).

    Article  ADS  CAS  Google Scholar 

  29. Zerangue, N., Arriza, J. L., Amara, S. G. & Kavanaugh, M. P. J. Biol. Chem. 270, 6433–6435 (1995).

    Article  CAS  Google Scholar 

  30. Volterra, A., Trotti, D., Tromba, C., Floridi, S. & Racagni, G. J. Neurosci. 14, 2924–2932 (1994).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zerangue, N., Kavanaugh, M. Flux coupling in a neuronal glutamate transporter. Nature 383, 634–637 (1996). https://doi.org/10.1038/383634a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/383634a0

  • Springer Nature Limited

This article is cited by

Navigation