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Pharmacology of GABA and Glycine Neurotransmission pp 79–99Cite as

The Molecular Architecture of GABAA Receptors

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 150))

Abstract

The structure of the GABAA receptor was unknown until 1987, when its subunits were revealed by cDNA cloning. Much general information on its molecular properties had accrued from biochemical and pharmacological analyses prior to then (reviewed by Stephenson 1988). Starting from purification on a benzodiazepine affinity column of a protein preparation which retained the multiple types of binding site previously identified in the native receptors (Sigel and Barnard 1984), followed by peptide sequencing, cDNA cloning led to the structure of the first 2 subunit types, α1 and β1 (Schofield et al. 1987). The topology of the subunits in the cell membrane (Fig. 1) was thus deduced and a superfamily of transmitter-gated ion channels became apparent (Barnard et al. 1987). This, the “Cys-loop” superfamily (see Fig. 1) (Cockroft et al. 1990; Karlin and Akabas 1995) is now known to contain five related receptor families (Barnard 1996): acetylcholine (nicotinic), 5-hydroxytryptamine3, GABA, glycine and glutamate (anion channel). The latter three, a set of anion channels, are more homologous to each other, sharing up to 27% amino acid sequence identity.

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  1. Institute of Pharmacology and Toxicology, ETH and University of Zürich, Winterthurerstr. 190, CH-8057, Zürich, Switzerland

    Hanns Möhler

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Barnard, E.A. (2001). The Molecular Architecture of GABAA Receptors. In: Möhler, H. (eds) Pharmacology of GABA and Glycine Neurotransmission. Handbook of Experimental Pharmacology, vol 150. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56833-6_2

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  • DOI: https://doi.org/10.1007/978-3-642-56833-6_2

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