Sodium- and chloride-dependent GABA transporter 1 (GAT-1) (GAT-1)

The Sodium- and chloride-dependent GABA transporter 1 (GAT-1) is a transmembrane protein that plays a pivotal role in regulating inhibitory neurotransmission within the central nervous system (UniProt P23978). Encoded by the SLC6A1 gene, GAT-1 is primarily responsible for the reuptake of gamma-aminobutyric acid (GABA) from the synaptic cleft into presynaptic neurons and surrounding glial cells (NCBI Gene 6529). This transport process is electrogenic and depends on the co-transport of sodium and chloride ions. By clearing GABA from the synapse, GAT-1 effectively terminates the inhibitory signal and maintains GABA homeostasis. Clinically, GAT-1 is a significant therapeutic target; its inhibition leads to increased extracellular GABA concentrations, which enhances GABAergic tone and provides anticonvulsant effects (StatPearls, Tiagabine). Mutations in the SLC6A1 gene are associated with various forms of epilepsy and neurodevelopmental disorders, highlighting its critical role in brain function (PubMed PMC6610389). Drugs like Tiagabine specifically target GAT-1 to treat partial seizures, though they must be managed carefully due to potential central nervous system side effects like dizziness and somnolence.

Other names

GAT-1SLC6A1GABA transporter 1Solute carrier family 6 member 1

Inhibition of GABA reuptake from the synaptic cleft into neurons and glia, increasing extracellular GABA levels and enhancing inhibitory neurotransmission.