Figure 1.

The mechanism of GABAergic neurotransmission. GABA is synthesised in the cytoplasm of the presynaptic terminal by GAD65 or GAD67 from glutamate supplied by adjacent glial cells via uptake of glutamine by the glutamine transporter and conversion to glutamate (1 to 4). GABA is then loaded into synaptic vesicles by VGAT (5) and released into the synaptic cleft via vesicle exocytosis (6). GABA can then bind to ionotropic GABA_A or GABA_C receptors (7), directly activating Cl⁻ flux across the postsynaptic membrane (8), or to metabotropic GABA_B receptors, indirectly activating Ca²⁺ or K⁺ ion channels via second messenger signalling (9). GABA is taken up from the synaptic cleft into glial cells via GAT 2/3 (10) for breakdown into glutamine (11) or into the presynaptic terminal via GAT-1 for recycling into synaptic vesicles (12).