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PMID: 9824848 Published · ppublish English Comparative Study Journal Article Review

The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.

Molecular neurobiology ·Vol. 18 ·No. 1 ·1998-08-00 ·Pages 35-86

Hevers W, Lüddens H

Abstract

The amino acid gamma-aminobutyric-acid (GABA) prevails in the CNS as an inhibitory neurotransmitter that mediates most of its effects through fast GABA-gated Cl(-)-channels (GABAAR). Molecular biology uncovered the complex subunit architecture of this receptor channel, in which a pentameric assembly derived from five of at least 17 mammalian subunits, grouped in the six classes alpha, beta, gamma, delta, sigma and epsilon, permits a vast number of putative receptor isoforms. The subunit composition of a particular receptor determines the specific effects of allosterical modulators of the GABAARs like benzodiazepines (BZs), barbiturates, steroids, some convulsants, polyvalent cations, and ethanol. To understand the physiology and diversity of GABAARs, the native isoforms have to be identified by their localization in the brain and by their pharmacology. In heterologous expression systems, channels require the presence of alpha, beta, and gamma subunits in order to mimic the full repertoire of native receptor responses to drugs, with the BZ pharmacology being determined by the particular alpha and gamma subunit variants. Little is known about the functional properties of the beta, delta, and epsilon subunit classes and only a few receptor subtype-specific substances like loreclezole and furosemide are known that enable the identification of defined receptor subtypes. We will summarize the pharmacology of putative receptor isoforms and emphasize the characteristics of functional channels. Knowledge of the complex pharmacology of GABAARs might eventually enable site-directed drug design to further our understanding of GABA-related disorders and of the complex interaction of excitatory and inhibitory mechanisms in neuronal processing.

MeSH Terms
Anesthetics/pharmacology Animals Barbiturates/pharmacology Benzodiazepines/pharmacology Binding Sites Chloride Channels/chemistry,classification,drug effects,physiology Convulsants/pharmacology Electrophysiology GABA Agonists/pharmacology GABA Antagonists/pharmacology Humans Ion Channel Gating Ion Transport Macromolecular Substances Mice Mice, Knockout Protein Conformation Protein Isoforms/chemistry,classification,drug effects,physiology Rats Receptors, GABA-A/chemistry,classification,drug effects,physiology Recombinant Proteins/metabolism Steroids/pharmacology Substrate Specificity gamma-Aminobutyric Acid/physiology
Chemicals
Anesthetics Barbiturates Chloride Channels Convulsants GABA Agonists GABA Antagonists Macromolecular Substances Protein Isoforms Receptors, GABA-A Recombinant Proteins Steroids Benzodiazepines gamma-Aminobutyric Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hevers W
Department of Psychiatry, University of Mainz, Germany.
Lüddens H
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Article Info
Journal
Molecular neurobiology
Abbr.
Mol Neurobiol
ISSN
0893-7648
DOI
10.1007/BF02741459
Published
1998-08-00
Pages
35-86
Language
English
Region
United States
NLM ID
8900963
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02741459 View journal details
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