Structural and functional basis for GABAA receptor heterogeneity

Levitan, Edwin S.; Schofield, Peter R.; Burt, David R.; Rhee, Lucy M.; Wisden, William; K�hler, Martin; Fujita, Norihisa; Rodriguez, Henry F.; Stephenson, Anne; Darlison, Mark G.; Barnard, Eric A.; Seeburg, Peter H.

Abstract

When γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in vertebrate brain, binds to its receptor it activates a chloride channel. Neurotransmitter action at the GABAA receptor is potentiated by both benzodiazepines and barbiturates which are therapeutically useful drugs (reviewed in ref. 1). There is strong evidence that this receptor is heterogeneous1–7. We have previously isolated complementary DNAs encoding an α- and a β-submit and shown that both are needed for expression of a functional GABAA receptor8. We have now isolated cDNAs encoding two additional GABAA receptor α-subunits, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating a molecular basis for it. These α-subunits are differentially expressed within the CNS and produce, when expressed with the β-subunit in Xenopus oocytes, receptor subtypes which can be distinguished by their apparent sensitivity to GABA. Highly homologous receptor subtypes which differ functionally seem to be a common feature of brain receptors.

Citation

Levitan, E. S., Schofield, P. R., Burt, D. R., Rhee, L. M., Wisden, W., Köhler, M., Fujita, N., Rodriguez, H. F., Stephenson, A., Darlison, M. G., Barnard, E. A., & Seeburg, P. H. (1988). Structural and functional basis for GABAA receptor heterogeneity. Nature, 335(6185), 76-79. https://doi.org/10.1038/335076a0

• Journal Article Type: Letter
• Acceptance Date: Jul 19, 1988
• Publication Date: Sep 1, 1988
• Deposit Date: Aug 5, 2016
• Journal: Nature
• Print ISSN: 0028-0836
• Electronic ISSN: 1476-4687
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 335
• Issue: 6185
• Pages: 76-79
• DOI: https://doi.org/10.1038/335076a0
• Keywords: General
• Public URL: http://researchrepository.napier.ac.uk/Output/327839