Meta-Biol

• Pathways

The GABA(A) receptor (GABR) family belongs to the ligand-gated ion channel superfamily (LGIC). Its endogenous ligand is gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. There are six alpha subunits (GABRA) (Garrett et al. 1988, Schofield et al. 1989, Hadingham et al. 1993, Edenberg et al. 2004, Hadingham et al. 1993, Yang et al. 1995, Wingrove et al. 1992, Hadingham et al. 1996), three beta subunits (GABRB) (Schofield et al. 1989, Hadingham et al. 1993, Wagstaff et al. 1991), 2 gamma subunits (GABRG) (Khan et al. 1993, Hadingham et al. 1995) and a theta subunit (Bonnert et al. 1999) characterised to date. GABA(A) functions as a heteropentamer, the most common structure being 2 alpha subunits, 2 beta subunits and a gamma subunit (2GABRA:2GABRB:GABRG). An alternative heteropentamer with much less affinity for GABA is 2GABRA:GABRB:GABRG:GABRQ (Bonnert et al. 1999). Upon binding of GABA, both GABR complexes conduct chloride ions through their pore, resulting in hyperpolarisation of the neuron. This causes an inhibitory effect on neurotransmission by reducing the chances of a successful action potential occurring.