Gamma-aminobutyric acid transporter (GAT) (GAT)

The GABA uptake system is a group of plasma membrane transporters responsible for the termination of GABAergic neurotransmission by removing gamma-aminobutyric acid (GABA) from the synaptic cleft (UniProt: P30531). This system primarily comprises four transporters: GAT-1, GAT-2, GAT-3, and BGT-1, which belong to the solute carrier 6 (SLC6) family of sodium- and chloride-dependent symporters (PubMed: 16402919). GAT-1 is the most abundant isoform in the brain and is predominantly located on presynaptic neuronal terminals, while GAT-3 is largely expressed on perisynaptic astrocytes (PubMed: 25839144). By regulating the concentration and duration of GABA in the extracellular space, these transporters play a critical role in controlling neuronal excitability and preventing excitotoxicity (StatPearls: NBK513311). Dysfunction of the GABA uptake system is linked to epilepsy, movement disorders, and psychiatric conditions like anxiety and schizophrenia (PubMed: 29051558). Pharmacological inhibition of GAT-1, notably by the drug tiagabine, increases the availability of GABA at synaptic and extrasynaptic receptors, providing an anticonvulsant effect (PubChem: CID 60648). Beyond epilepsy, the system is a target for research in treating chronic pain and sleep disorders due to its role in modulating inhibitory tone. Therapeutic challenges include achieving isoform specificity to minimize side effects like sedation or motor impairment associated with broad GABAergic elevation.

Other names

GABA uptake systemGABA transporterSodium- and chloride-dependent GABA transporterSLC6A transportersGABA reuptake system

Inhibition of GABA reuptake from the synaptic cleft into neurons and glia, thereby increasing the concentration and residence time of GABA in the extracellular space to enhance inhibitory neurotransmission.