GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the brain. Its production, release, reuptake, and metabolism all occur in the nervous system¹.

The GABA transmitter interacts with two major types of receptors: ionotropic GABA_A receptors (GABA_AR) and metabotropic receptors (GABA_BR). GABA_ARs belong to the ligand-gated ion channel superfamily². GABA inhibits the activity of signal-receiving neurons by interacting with the GABA_A receptor on these cells³. Binding of GABA to its GABA_A receptor results in conformational changes that open a Cl^- channel, producing an increase in membrane conductance that results in inhibition of neural activity².

GABA_ARs are heteropentamers, in which all five subunits contribute to the pore formation. To date, eight subunit isoforms have been cloned: α, β, γ, δ, ε, π, θ, and ρ¹. Six α subunit isoforms have been found to exist in mammals (α1-α6). In most cases, native GABA_A receptors consist of 2α, 2β, and 1γ subunits. The α subunit is the most common and is expressed ubiquitously. It determines the affinity of GABA_ARs for allosteric ligands.

Each subtype has a unique regional expression in the brain, and individual neurons often express multiple subtypes⁴. For example, the α4 subunit is detected in the hippocampus, cortex, olfactory bulb and in the basal forebrain⁵.