GABA_A-ρ Receptors in the CNS: Their Functional, Pharmacological, and Structural Properties in Neurons and Astroglia

Gamma-aminobutyric acid (GABA) is known as the main inhibitory transmitter in the central nervous system (CNS), where it hyperpolarizes mature neurons through activation of GABAA receptors, pentameric complexes assembled by combination of subunits (α1–6, β1–3, γ1–3, δ, ε, θ, π and ρ1–3). GABAA-ρ subunits were originally described in the retina where they generate non-desensitizing Cl- currents that are insensitive to bicuculline and baclofen. However, now is known that they are widely expressed throughout the brain including glial cells. For example, whole-cell patch-clamp recordings demonstrated the functional expression of GABAA-ρ receptors in primary cultures of cerebellar astrocytes, as well as in cerebellar ependymal cells and striatal astrocytes. In these cells GABA-currents were partially blocked by TPMPA and insensitive to barbiturates. These receptors are proposed to be involved in extrasynaptic communication and dysfunction of the signaling is accompanied by reduced expression of GABAA-ρ receptors in Huntington’s disease and autism spectrum disorders (ASD). Thus, the aim of this review is to present an overview about GABAA-ρ receptors including their structure and function, as well as their importance in the excitatory/inhibitory (E/I) balance in neurodevelopment and in disease.