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Sodium- and chloride-dependent GABA transporter 2 (GAT2), encoded by the SLC6A13 gene, is a transmembrane protein belonging to the solute carrier family 6 (UniProt P48066). It functions as a symporter that moves gamma-aminobutyric acid (GABA) and betaine across cell membranes, driven by the electrochemical gradient of sodium and chloride ions (NCBI Gene 6540). While other GABA transporters like GAT1 are concentrated in neurons, GAT2 is uniquely expressed in the liver, kidney, and the brain's barrier tissues, such as the leptomeninges and choroid plexus (Schousboe et al., 2004, PMID: 15556488). This distribution suggests that GAT2 plays a critical role in regulating GABA levels in the systemic circulation and at the blood-brain barrier interface. In pathological states, GAT2 dysfunction or modulation is linked to epilepsy and seizure susceptibility, as it influences the availability of the primary inhibitory neurotransmitter in the central nervous system (Zhou et al., 2012, PMID: 22403564). Pharmacologically, GAT2 is a target for experimental anticonvulsants like EF1502, although most current clinical agents are selective for GAT1. Research into GAT2-specific inhibitors aims to provide new avenues for seizure control, particularly for patients refractory to standard GABAergic medications. Additionally, its role in betaine transport links it to osmoregulation and metabolic health in peripheral organs.
Inhibition of GABA reuptake
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