GABA_A and GABA_A-ρ Receptors

GABA_A and GABA_A-ρ receptors are ligand-gated ion channels, which, along with the G-protein coupled GABA_B receptors, mediate the effects of GABA. GABA is the major inhibitory neurotransmitter in the central nervous system and is present in interneurons and projection neurons throughout the brain, and also plays important roles in the peripharal nervous system.

GABA_A receptors are formed from five subunits and are permeable to Cl^- ions and, to a lesser extent, bicarbonate ions (HCO^-). These receptors have extremely complex pharmacological profiles due to the presence of multiple subtypes of each subunit, splice variants of those subtypes and specific binding sites for multiple different compound classes. The specificity of individual ligands is determined by the subunit conformation of a single receptor.

GABA_A and GABA_A-ρ Receptor Targets

Related Targets

In mammals there are 8 subunit families, some of which have multiple subtpes; 6α, 3β, 3γ, 1δ, 3ρ, 1ε, 1π and 1θ. The majority of endogenous GABA_A receptors in the human brain are composed of two α-subunits, two β-subunits and a single γ-subunit. A subclass of GABA_A receptors, GABA_A-ρ receptors, are homomeric channels formed exclusively from ρ-subunits. These receptors were previously known as GABA_C receptors.

All GABA_A subunits have a similar structure with a long N-terminal extracellular domain, four a-helical transmembrane domains (M1 to M4) and a long intracellular loop between M3 and M4. A variety of proteins associate with the large intracellular M3-M4 loop of GABA_A and GABA_A-ρ receptors and influence the trafficking, cell surface expression, internalization and function of the receptors. For example, the M3/M4 loop contains a phosphorylation site for Protein Kinase C in the majority of GABA_A receptor subunits; the presence of this phosphorylation site is splice variant-dependent.