GABA_A receptors

GABA (γ-aminobutyric acid) is the essential inhibitory neurotransmitter in the vertebrate brain. It interacts with three kinds of receptors: Class A¹, B² and C³. While GABA_AR and GABA_CR are ligand-gated Cl^– channels, GABA_BR can activate other channels via G protein.

The binding of GABA transmitter to the GABA_AR opens the Cl^– channels which leads to an increase in membrane conductance and an inhibition of neuronal activity.

The GABA_AR is composed of 6 subunits: α, β, γ, ε and π⁴. Each one is encoded by a few genes. There are 6 different genes for the α subunit, 3 for β and γ, and 1 for the others. In most cases, the receptor is assembled to a pentamer⁵ of 2α, 2β and 1γ subunit when each one consists of 4 putative transmembrane domains, with a long N-terminus and a short C-terminus tail, both extracellular.

The inhibition mediated by GABA is also induced when other agents interact with GABA_AR.

The receptor possesses modulatory binding sites for antiepileptic drugs, anxiolitics⁶ sedative and anesthetic agents and this makes it a study of therapeutic importance.

References

1. Macdonald, R. L. and Olsen, R. W. (1994) Annu. Rev. Neurosci. 17, 569.
2. Bowery, N. G. (1993) Annu. Rev. Pharmacol. Toxicol. 33, 109.
3. Johnston, G.A.R. (1994) Prog. Brain Res. 100, 61.
4. Frances M. Ashcroft (2000) Ion Channels and Disease. Academic Press.
5. Tretter, V. et al. (1997) J. Neurosci. 17, 2728.
6. Polenzani, L. et al. (1991) Proc. Nat l. Acad. Sci. USA. 88, 4318.