γ-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter. It is involved in roughly 40% of inhibitory synapses^1,2.

GABA acts through two receptors, GABA(A) and GABA(B). To date, nineteen different GABA(A) subunits have been identified and divided in eight subunits: α (1-6), β (1-3), γ (1-3), δ, ε, ρ (1-3), θ and π. For some of the subunits, alternative splicing further increases the number of existing receptor types. They all have extracellular N- and C-termini and four transmembrane domains¹.

Three ρ subunits have been detected: GABA(A) ρ1, GABA(A) ρ2 and GABA(A) ρ3. Like all GABA(A) receptors the ρ subunits also assemble into a pentameric structure forming a Cl^- channel. However, in contrast to all other GABA(A) subunits they mostly form homomeric entities. The GABA(A) ρ subunits display different pharmacological characteristics and were therefore once referred to as GABA(C) receptors. GABA(A) and GABA(B) respectively respond to bicuculline and baclofen, whereas ρ subunits are insensitive to either drug^3-7. In addition, ρ subunits also display different electrophysiological properties, and are significantly more sensitive to GABA^3,5,6,8.

ρ subunits are highly expressed in the retina and it was believed that they are only expressed in that area. They are however, also expressed in central and peripheral nervous systems, as well as in the gastrointestinal and cardiovascular systems¹.