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Journal of Molecular Neuroscience

, Volume 67, Issue 2, pp 343–351 | Cite as

The α5-Containing GABAA Receptors—a Brief Summary

  • Fatin H. Mohamad
  • Ahmad Tarmizi Che HasEmail author
Article

Abstract

GABAA receptors are the major inhibitory neurotransmitter receptor in the human brain. The receptors are assembled from combination of protein subunits in pentameric complex which may consist of α1–6, β1–3, γ1–3, ρ1–3, δ, ε, θ, or π subunits. There are a theoretical > 150,000 possible assemblies and arrangements of GABAA subunits, although only a few combinations have been found in human with the most dominant consists of 2α1, 2β2, and 1γ2 in a counterclockwise arrangement as seen from the synaptic cleft. The receptors also possess binding sites for various unrelated substances including benzodiazepines, barbiturates, and anesthetics. The α5-containing GABAARs only make up ≤ 5% of the entire receptor population, but up to 25% of the receptor subtype is located in the crucial learning and memory-associated area of the brain—the hippocampus, which has ignited myriads of hypotheses and theories in regard to its role. As well as exhibiting synaptic phasic inhibition, the α5-containing receptors are also extrasynaptic and mediate tonic inhibition with continuously occurring smaller amplitude. Studies on negative-allosteric modulators for reducing this tonic inhibition have been shown to enhance learning and memory in neurological disorders such as schizophrenia, Down syndrome, and autism with a possible alternative benzodiazepine binding site. Therefore, a few α5 subunit-specific compounds have been developed to address these pharmacological needs. With its small population, the α5-containing receptors could be the key and also the answer for many untreated cognitive dysfunctions and disorders.

Keywords

GABAA receptors Extrasynaptic Tonic inhibition Cognitive dysfunction 

Notes

Funding Information

This review work was funded by the Research University Grant 1001/PPSP/812186, Universiti Sains Malaysia (USM).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosciences, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

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