γ-Aminobutyric acid

γ-aminobutyric acid (GABA) is an amino acid derivate, synthesized from glutamate by the pyridoxal-L-phosphate (PLP)-dependent enzyme, glutamate decarboxylase (GAD)¹. GABA provides the primary inhibitory signaling in the adult mammalian brain (CNS), and, to some degree of controversy, exerts a depolarizing response in the developing brain².

GABA is an agonist of two main receptor classes in the CNS: GABA_A, an ionic ligand gated channel, and GABA_B, a metabotrophic, G-protein coupled receptor. GABA_A is assembled by 5 out of 16 possible subunits with α, β and either a γ or a δ (2:2:1 stoichiometry) being the most common. With an EC₅₀ between 3 - 12μM it interacts with GABA to allow either an influx or an efflux of Cl^- ions, into and out of the cell, respectively³. GABA_B is a heterodimer comprised of the subunits GABA_B1 and GABA_B2. It reduces neurotransmitter release by inhibiting Ca²⁺ channels when activated presynaptically, and facilitates inward rectifying potassium channels, postsynaptically¹.

GABA deficiency is often the prime cause for epilepsy, with other notably disorders being autism⁴, spasticity, anxiety disorders, schizophrenia, and stiff-person syndrome⁵.