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Insensitivity to anaesthetic agents conferred by a class of GABAA receptor subunit

Nature volume 385, pages 820–823 (1997)Cite this article

Abstract

A common feature of general anaesthetic agents is their ability to potentiate neuronal inhibition through GABAA (γ-aminobutyric acid) receptors1. At concentrations relevant to clinical anaesthesia, these agents cause a dramatic stimulation of the chloride currents that are evoked by the binding of the natural ligand, GABAA. Although there is widespread evidence that the sensitivity of GABAA receptors to anaesthetic agents is heterogeneous2–4, the structural basis of these differences is largely unknown. Variations in subunit composition can have profound effects on the sensitivity of GABAA receptors to modulatory agents such as benzodiazepines5. However, strict subunit specificity has not been demonstrated for the potentiating effects of anaesthetic agents6–10. Here we describe a new class of human GABAA receptor subunit (η) that can assemble with α- and β-subunits and confer an insensitivity to the potentiating effects of intravenous anaesthetic agents. The η-subunit also abolishes the normal outward rectification of recombinant receptors in which it assembles. The expression pattern of this subunit in the brain suggests a new target for manipulation of neuronal pathways within the basal ganglia.

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References

  1. Franks, N. P. & Lieb, W. R. Nature 367, 607–614 (1994).

    Article  ADS  CAS  Google Scholar 

  2. Bureau, M. N. & Olsen, R. W. J. Neurochem. 61, 1479–1491 (1993).

    Article  CAS  Google Scholar 

  3. Morrow, A. L., Pace, J. R., Purdy, R. H. & Paul, S. M. Mol. Pharmacol. 37, 263–270 (1990).

    CAS  PubMed  Google Scholar 

  4. Harris, B., Wong, G. & Skolnick, P. J. Pharmacol. Exp. Ther. 265, 1392–1398 (1993).

    CAS  PubMed  Google Scholar 

  5. Pritchett, D. B. et al. Nature 338, 582–585 (1989).

    Article  ADS  CAS  Google Scholar 

  6. Thomson, S. A., Whiting, P. J. & Wafford, K. A. Br. J. Pharmacol. 117, 521–527 (1996).

    Article  Google Scholar 

  7. Hadingham, K. L. et al. Mol. Pharmacol. 44, 1211–1218 (1993).

    CAS  PubMed  Google Scholar 

  8. Puia, G. et al. Neuron 4, 759–765 (1990).

    Article  CAS  Google Scholar 

  9. Sanna, E. et al. J. Pharmacol. Exp. Ther. 274, 353–360 (1995).

    CAS  PubMed  Google Scholar 

  10. Mihac, S. J., Whiting, P. J. & Harris, R. A. Eur. J. Pharmacol. 268, 209–214 (1994).

    Article  Google Scholar 

  11. Whiting, P. J., McKernan, R. M. & Wafford, K. A. Int. Rev. Neurobiol. 38, 95–138 (1995).

    Article  CAS  Google Scholar 

  12. Bell, K., Churchhill, L. & Kalivas, P. W. Synapse 20, 10–18 (1995).

    Article  CAS  Google Scholar 

  13. Wisden, W., Laurie, D. J., Monyer, H. & Seeburg, P. H. J. Neurosci. 12, 1040–1062 (1992).

    Article  CAS  Google Scholar 

  14. Schmieden, V., Kuhse, J. & Betz, H. EMBO J. 11, 2025–2032 (1992).

    Article  CAS  Google Scholar 

  15. Saxena, N. C. & Macdonald, R. L. J. Neurosci. 14, 7077–7086 (1994).

    Article  CAS  Google Scholar 

  16. Verdoorn, T. A., Draguhn, A., Ymer, S., Seeburg, P. H. & Sakmann, B. Neuron 4, 919–928 (1992).

    Article  Google Scholar 

  17. Davies, P. A., Kirkness, E. F. & Hales, T. G. Br. J. Pharmacol. 120, 899–909 (1997).

    Article  CAS  Google Scholar 

  18. Gray, R. & Johnston, D. J. Neurophysiol. 54, 134–142 (1985).

    Article  CAS  Google Scholar 

  19. Segal, M. & Barker, J. L. J. Neurophysiol. 51, 500–515 (1984).

    Article  CAS  Google Scholar 

  20. Bormann, J., Hamill, O. P. & Sakmann, B. J. Physiol. (Lond.) 385, 243–286 (1987).

    Article  CAS  Google Scholar 

  21. Gage, P. W. & Chung, S. H. Proc. R. Soc. Lond. B 255, 167–172 (1994).

    Article  ADS  CAS  Google Scholar 

  22. Korpi, E. R. & Luddens, H. Mol. Pharmacol. 44, 87–92 (1993).

    CAS  PubMed  Google Scholar 

  23. Peters, J. A., Kirkness, E. F., Callachan, H., Lambert, J. J. & Turner, A. J. Br. J. Pharmacol. 94, 1257–1269 (1988).

    Article  CAS  Google Scholar 

  24. Zhu, W. J., Wang, J. F., Krueger, K. E. & Vicini, S. J. Neurosci. 16, 6648–6656 (1996).

    Article  CAS  Google Scholar 

  25. Bergman, H., Wichmann, T. & DeLong, M. R. Science 249, 1436–1438 (1990).

    Article  ADS  CAS  Google Scholar 

  26. Goetz, C. G. & Diederich, N. J. Nature Med. 2, 510–514 (1996).

    Article  CAS  Google Scholar 

  27. Adams, M. D. et al. Nature (suppl.) 377, 3–174 (1995).

    CAS  Google Scholar 

  28. Tokunaga, K. et al. Cancer Res. 47, 5616–5619 (1987).

    PubMed  Google Scholar 

  29. Buller, A. L., Hastings, G. A., Kirkness, E. F. & Fraser, C. M. Mol. Pharmacol. 46, 858–865 (1994).

    CAS  PubMed  Google Scholar 

  30. Adodra, S. & Hales, T. G. Br. J. Pharmacol. 115, 953–960 (1995).

    Article  CAS  Google Scholar 

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Author notes

  1. Paul A. Davies and Tim G. Hales: Department of Anesthesiology, Brain Research Institute, UCLA Medical Center, Los Angeles, California 90095, USA

Authors and Affiliations

  1. The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland, 20850, USA

    Paul A. Davies, Mike C. Hanna, Tim G. Hales & Ewen F. Kirkness

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  1. Paul A. Davies
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  2. Mike C. Hanna
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  3. Tim G. Hales
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  4. Ewen F. Kirkness
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Davies, P., Hanna, M., Hales, T. et al. Insensitivity to anaesthetic agents conferred by a class of GABAA receptor subunit. Nature 385, 820–823 (1997). https://doi.org/10.1038/385820a0

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