Overview of Synaptic Neurotransmission: GABAergic Inhibition
The long-term stability and function of neuronal networks is dependent on a maintained balance between excitatory and inhibitory synaptic transmission. The major inhibitory neurotransmitter in the central nervous system is gamma-aminobutyric acid (GABA), which is converted from glutamate by the enzyme Glutamic Acid Decarboxylase (GAD). Similar to glutamate receptors (GluRs), GABA receptors are ionotropic (GABA-A) or metabotropic (GABA-B). GABA-A receptors are heteropentameric ligand-gated ion channels that selectively permit the influx of Cl- and HCO3- ions to decrease membrane excitability. Extremely heterologous with at least nineteen known subunit genes, GABA-A receptors mediate the majority of fast synaptic inhibition. Metabotropic GABA-B receptors are G protein-coupled heterodimers of GABA-B1 and GABA-B2. They are expressed on both the presynaptic and postsynaptic terminals where they inhibit neurotransmitter release and induce cell membrane hyperpolarization, respectively. A third group of receptors was originally classified as GABA-C. These receptors are now considered as members of the GABA-A family.