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.

  • Letter
  • Published:

Hippocampal GABA transporter function in temporal-lobe epilepsy

Nature volume 376, pages 174–177 (1995)Cite this article

Abstract

ELECTROPHYSIOLOGICAL studies of human temporal-lobe epilepsy suggest that a loss of hippocampal GABA-mediated inhibition may underlie the neuronal hyperexcitability1–3. However, GABA (γ-aminobutyric acid)-containing cells are preserved4and GABA receptors are maintained in the surviving hippocampal neurons5. Diminished GABA release may therefore mediate the loss of inhibition. Here we show that, in the human brain, potassium-stimulated release of GABA was increased, and glutamate-induced, calcium-independent release of GABA was markedly decreased, in epileptogenic hippocampi, in contrast with contra-lateral, non-epileptogenic hippocampi. The glutamate-induced GABA release in vivo was transporter-mediated in rats. Furthermore, in amygdala-kindled rats, a model for human epilepsy, a decrease in glutamate-induced GABA release was associated with a 48% decrease in the number of GABA transporters. These data suggest that temporal-lobe epilepsy is characterized in part by a loss of glutamate-stimulated GABA release that is secondary to a reduction in the number of GABA transporters.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Isokawa, M., Avanzini, G., Finch, D. M., Babb, T. L. & Levesque, M. F. Epilepsy Res. 9, 242–250 (1991).

    Article  CAS  Google Scholar 

  2. Knowles, W. D., Awad, I. A. & Nayel, M. H. Epilepsia 33, 601–609 (1992).

    Article  CAS  Google Scholar 

  3. Williamson, A. Clin. Neurosci. 2, 47–52 (1994).

    Google Scholar 

  4. Babb, T. L., Pretorius, J. K., Kufer, W. R. & Crandall, P. H. J. Neurosci. 9, 2562–2574 (1989).

    Article  CAS  Google Scholar 

  5. Johnson, E. et al. Neurology 42, 811–815 (1992).

    Article  CAS  Google Scholar 

  6. During, M. J. & Spencer, D. D. Lancet 341, 1607–1610 (1993).

    Article  CAS  Google Scholar 

  7. Radian, R., Ottersen, O. P., Storm-Mathisen, J., Castel, M. & Kanner, B. I. J. Neurosci. 10, 1319–1330 (1990).

    Article  CAS  Google Scholar 

  8. Pin, J.-P. & Bockaert, J. J. Neurosci. 9, 648–656 (1989).

    Article  CAS  Google Scholar 

  9. Harris, K. M. & Miller, R. J. Brain Res. 482, 23–33 (1989).

    Article  CAS  Google Scholar 

  10. Szerb, J. C. J. Neurochem. 39, 850–858 (1982).

    Article  CAS  Google Scholar 

  11. McNamara, J. O., Byrne, M. C., Dasheiff, R. M. & Fitz, J. G. Prog. Neurobiol. 15, 139–159 (1980).

    Article  CAS  Google Scholar 

  12. Simpson, M. D., Slater, P., Deakin, J. F., Royston, M. C. & Sken, W. J. Neurosci. Lett. 107, 211–215 (1988).

    Article  Google Scholar 

  13. Morrison, P. F. et al. in Microdialysis in the Neurosciences (eds Robinson, T. E. & Justice, J. B.) 47–80 (Elsevier, Amsterdam, 1991).

    Book  Google Scholar 

  14. Braestrup, C. et al. J. Neurochem. 54, 639–646 (1990).

    Article  CAS  Google Scholar 

  15. Drejer, J., Honore, T. & Schousboe, A. J. Neurosci. 7, 2910–2916 (1987).

    Article  CAS  Google Scholar 

  16. Gallo, V., Patrizio, M. & Levi, G. Glia 4, 245–255 (1991).

    Article  CAS  Google Scholar 

  17. Geddes, J. W. et al. Expl Neurol. 108, 214–220 (1990).

    Article  CAS  Google Scholar 

  18. McDonald, J. W. et al. Ann. Neurol. 29, 325–332 (1991).

    Article  Google Scholar 

  19. de Lanerolle, N. C., Brines, M., Williamson, A., Kim, J. H. & Spencer, D. D. in the Dentate Gyrus and its Role in Seizures (eds Ribak, C. E., Gall, C. M. & Moody, I.) 235–250 (Elsevier, Amsterdam, 1991).

    Google Scholar 

  20. During, M. J. et al. Epilepsia 33, Suppl. 3, 83 (1992).

    Google Scholar 

  21. Williamson, A., Telfcian, A. & Spencer, D. D. J. Neurophysiol. (in the press).

  22. Horton, R. W., Collins, J. F., Anlezark, G. M. & Meldrum, B. S. Eur. J. Pharmac. 59, 75–83 (1979).

    Article  CAS  Google Scholar 

  23. Gonsalves, S. F., Twitchell, B., Harbough, R. E., Krogsgaard-Larsen, P. & Schousboe, A. Epilepsy Res. 4, 34–41 (1989).

    Article  CAS  Google Scholar 

  24. Alger, B. E. & Nicoll, R. A. J. Physiol. 328, 125–141 (1982).

    Article  CAS  Google Scholar 

  25. Mangano, R. M. & Schwarcz, R. Brain Res. Bull. 10, 47–51 (1983).

    Article  CAS  Google Scholar 

  26. During, M. J., Craig, J. S., Hernandez, T. O., Anderson, G. M. & Gallagher, D. W. Brain Res. 584, 36–44 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Pharmacology and Neurogenetics Laboratory, Sections of Neurosurgery and Endocrinology, Departments of Surgery and Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06510, USA

    Matthew J. During, Kathryn M Ryder & Dennis D. Spencer

Authors
  1. Matthew J. During
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn M Ryder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dennis D. Spencer
    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

During, M., Ryder, K. & Spencer, D. Hippocampal GABA transporter function in temporal-lobe epilepsy. Nature 376, 174–177 (1995). https://doi.org/10.1038/376174a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/376174a0

This article is cited by

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