GABA(A) Receptor Antagonist Explorer Kit

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_Areceptors (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 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 consists of 2α, 2β, and 1δ subunits. The α subunit is the most common and is expressed ubiquitously. It determines the affinities of GABA_ARs for allosteric ligands.

Each subtype has a unique regional expression in the brain, and individual neurons often express multiple subtypes.⁴ The α1 subunit is highly expressed in adulthood while the α2 subunit is highly expressed very early in rat brain development. Failure to complete the normal transition between the α-subunits that are highly expressed in early development (α2, α3, and α5) and those expressed in adulthood (α1) is suggested to play a major role in the development of temporal lobe epilepsy⁵.