The diversity of GABAA receptors

  title={The diversity of GABAA receptors},
  author={Wulf Hevers and Hartmut L{\"u}ddens},
  journal={Molecular Neurobiology},
The amino acid γ-aminobutyric-acid (GABA) prevails in the CNS as an inhibitory neurotrans-mitter 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 α, β, γ, δ, ε, and ρ, permits a vast number of putative receptor isoforms. The subunit composition of a particular receptor… 
Assembly of GABAA receptors (Review)
The occurrence of a defined subunit stoichiometry and arrangement in αβγ receptors strongly indicates that assembly of GABAA receptors proceeds via defined pathways, but no unequivocal assembly mechanism has been identified.
Pharmacology of the GABAA Receptor
This chapter focuses on the relationship between receptor architecture and pharmacology of a large number of clinically relevant compounds such as benzodiazepines, barbiturates, anesthetics, neurosteroids and alcohols.
GABAA receptors: structure, function, pharmacology, and related disorders
This review aims to summarize the current understanding of the structural, physiological, and pharmacological properties of GABAARs, as well as shedding light on the most common associated disorders.
Analysis of γ-Aminobutyric Acid (GABA) Type A Receptor Subtypes Using Isosteric and Allosteric Ligands
  • R. Olsen
  • Biology, Chemistry
    Neurochemical Research
  • 2014
The channel blocker picrotoxin identified a noncompetitive channel blocker site in GABAARs, which is located in the transmembrane channel pore, whereas the GABA agonist site is in the extracellular domain at subunit interfaces, a site useful for low energy coupled conformational changes of the functional channel domain.
GABAA receptors: Subtypes provide diversity of function and pharmacology
A novel GABAA receptor pharmacology: drugs interacting with the α+β‐ interface
Several benzodiazepine site ligands have been identified that selectively interact with GABAA receptor subtypes containing α2βγ2, α3 βγ2 or α5βγ 2 subunits, which indicates that the different α subunit types present in these receptors convey sufficient structural differences to the benzdiazepine binding site to allow specific interaction with certain benzodiazine siteligands.
Pharmacological Properties of GABAA Receptors Containing γ1 Subunits
Modulation of GABA-induced chloride currents (IGABA) was studied at GABA concentrations eliciting 5 to 10% of the maximal response, and flunitrazepam and 2-phenyl-4-(4-ethyl-piperidinyl)-quinoline-quinoline at 1 μM concentrations were able to significantly enhance IGABA in α1β2γ1 receptors.


Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology
The isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed γ2, which shares approximately 40% sequence identity with α-and β-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS.
GabaA Receptors: Pharmacology, Behavioral Roles, and Motor Disorders
Besides their involvement in anxiolysis and sedation, GABAA receptors clearly have an impact on motor coordination, but with the possible exception of the alcohol-and BZ-sensitive alcohol non-tolerant (ANT) rat line, it is not well documented whether a genetic alteration in this receptor system is directly involved in the impairment of animal or human motor activity.
Structural and functional basis for GABAA receptor heterogeneity
Two additional cDNAs encoding two additional GABAA receptor α-subunits are isolated, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating the molecular basis for it.
Molecular biology of GABAA receptors
  • R. Olsen, A. Tobin
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1990
Subpopulations of GABAA receptors with different cellular and regional locations show differential sensitivity to GABA, to modulators like steroids, to physiological regulation, to disease processes, and to pharmacological manipulation by drugs such as benzodiazepines.
Stoichiometry of a Recombinant GABAA Receptor
It is concluded that the recombinant α1β2γ2 GABAA receptor is a pentamer composed of two α subunits, two β sub units, and one γ subunit, consistent with the interpretation that the leucine mutation increased the GABA sensitivity in proportion to the number of incorporated mutant subunits.
Modulation of GABAA receptors by tyrosine phosphorylation
Here, GABAA receptors consisting of α1, β1 and γ2L sub-units, coexpressed in mammalian cells with the tyrosine kinase vSRC (the transforming gene product of the Rous sarcoma virus), were phosphorylated on tyrosin residues within the γ 2L and β1 subunits.
Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties.
It is concluded that murine beta 1 subunits can form functional ion channels that are not gated by GABA but can be closed by some noncompetitive GABA antagonists.
Cerebellar GABAA receptor selective for a behavioural alcohol antagonist
It is concluded that this α-subunit is part of a cerebellar receptor subtype, selective for Rol5-4513 (refs 17, 18), an antagonist of alcohol-induced motor incoordination and ataxia, and photoaffinity-labelled with benzodiazepines.
Molecular mechanisms of the partial allosteric modulatory effects of bretazenil at gamma-aminobutyric acid type A receptor.
Drug-induced modifications of GABA-activated Cl- currents in native GABAA receptors of cortical neurons in primary cultures and in recombinant GAB AA receptors transiently expressed in transformed human embryonic kidney cells (293) after transfection with cDNAs encoding different molecular forms of alpha, beta, and gamma subunits of G ABAA receptors are studied.