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Diversity in Structure, Pharmacology, and Regulation of GABAA Receptors

  • Chapter
The GABA Receptors

Part of the book series: The Receptors ((REC))

Abstract

As the main inhibitory neurotransmitter in the brain, GABA is essential for the overall balance between neuronal excitation and inhibition. By acting on GABAA receptors, which are ligand-gated chloride channels, GABA mediates the principal fast inhibitory synaptic transmission. GABA exerts a ubiquitous influence largely by local feedback and feedforward circuits affecting a multitude of CNS functions. Adaptation of GABA-ergic transmission to various biological requirements, in particular to developmental maturation and cell-type specific signal transmission, is achieved by the expression of a multitude of structurally distinct GABAA receptors in the vertebrate brain. Receptor heterogeneity arises from a repertoire of at least 17 subunits, which can be grouped by the degree of sequence homology into 6α, 4β, 4γ, 1δ, and 2ρ subunits. The combinatorial assembly of these subunits (and splice variants of several of them) into a presumably pentameric heterooligomeric structure results in diverse receptor subtypes (for review, see Barnard, 1995; Luddens et al., 1995; Möhler et al., 1995a,b; Sieghart, 1995; Smith and Olsen, 1995). The most prevalent types of GABAA receptors have recently been identified and allocated to particular neuronal circuits. Apart from the physiological role in neuron-specific signal transduction (Table 1), GABAA receptor heterogeneity is of major pharmacological relevance. Many neuroactive drugs act on GABAA receptors, in particular ligands of the benzodiazepine (BZ) site, which are in clinical use for the treatment of anxiety, insomnia, muscle spasms, and epilepsy.

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Authors
  1. H. Möhler
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  2. D. Benke
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  3. J. Benson
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  4. B. Lüscher
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  5. U. Rudolph
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  6. J. M. Fritschy
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Editors and Affiliations

  1. Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical School, Kansas City, KS, USA

    S. J. Enna

  2. Department of Pharmacology, The Medical School Edgbaston, University of Birmingham, UK

    Norman G. Bowery

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Möhler, H., Benke, D., Benson, J., Lüscher, B., Rudolph, U., Fritschy, J.M. (1997). Diversity in Structure, Pharmacology, and Regulation of GABAA Receptors. In: Enna, S.J., Bowery, N.G. (eds) The GABA Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2597-1_2

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