(G)-aminobutyric acid (GABA) is an amino acid derivate, synthesized from glutamate by the pyridoxal-L-phosphate (PLP)-dependent enzyme, glutamate decarboxylase (GAD). 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 brain.
GABA is an agonist of two main receptor classes in the CNS: GABAA, an ionic ligand gated channel, and GABAB, a metabotrophic, G-protein coupled receptor. GABAA is assembled by 5 out of 16 possible subunits with (A), (B) and either a (G) or a (D) (2:2:1 stoichiometry) being the most common. With an EC50 between 3 to 12 micro M it interacts with GABA to allow either an influx or an efflux of Cl- ions into and out of the cell, respectively.
Bicuculline (BIC) is a competitive allosteric inhibitor of GABAA-induced currents with an IC50 of 1-3 micro M. BIC has been employed to model epileptic seizures in hippocampal slices; to induce schizophrenia-like symptoms in the pre-frontal cortex; and is an essential research tool in the study of various psychomotor and behavioral defects.
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