GABA signaling in brain
GABA signaling in brain Gamma-aminobutyric acid ( GABA ) is the most abundant inhibitoryneurotransmitter in the mammalian brain, where it is widely distributed.. GABAtransmission is present in the interneurons that modulate local neuronal circuitry,including noradrenergic, dopaminergic, and serotonergic neurons . GABA in GABAergic terminals is formed from Glutamic acid in an enzymaticreaction mediated by Glutamic acid decarboxylases 1 and 2 ( GAD1 and GAD2), using pyridoxal phosphate as cofactor , . After beingreleased into the synapses, GABA is inactivated by reuptake into presynapticterminals or into glial cells mediated by GABA transporters (GATs). GAT-1 isconsidered to be a neuronal transporter. GAT-2 and SLC6A11 (GAT-3) arebelieved to be glial transporters . GABA is bound to GABAergic receptors. GABAergic receptors are represented bytwo main types, GABA-A receptor and Galpha(i)-specific GABA-B GPCRs, Thetwo types are characteryzed by different distribution on the surface of neurons.GABA-A receptor s are ionotropic and mostly postsynaptic receptors mainly locatedat the apical dendrite of the neurons, causing the fast inhibitory postsynapticpotential. It is essential for brain development and behavioral actions , . Galpha(i)-specific GABA-B GPCRs may be localizatedon on presynaptic terminal soma and on postsynaptic neurone. Galpha(i)-specificGABA-B GPCRs are metabotropic receptors coupled to G-protein alpha-i family.Pre-synaptic Galpha(i)-specific GABA-B GPCRs inhibit neurotransmitter release bydown-regulating high voltage activated calcium channels, whereas postsynapticGalpha(i)-specific GABA-B GPCRs decrease neuronal excitability by activating aprominent inwardly rectifying potassium (Kir) conductance that underlies the lateinhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but alsoin hippocampal long-term potentiation, slow wave sleep, muscle relaxation andantinociception .