Sodium- and chloride-dependent betaine transporter (BGT1) (BGT1)

The Human betaine/GABA transporter 1 (BGT1), encoded by the SLC6A12 gene, is a sodium- and chloride-dependent symporter that mediates the cellular uptake of the osmolyte betaine and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) [1, 16]. It is predominantly expressed in the liver and kidney, where it plays a vital role in osmoregulation by accumulating betaine to protect cells from hyperosmotic stress [14, 16]. In the central nervous system, BGT1 is located primarily in glial cells and the leptomeninges, contributing to the regulation of extrasynaptic GABA levels [7, 16]. Although its expression in the brain is significantly lower than that of other GABA transporters like GAT1, BGT1 has emerged as a potential therapeutic target for epilepsy [5, 9]. Inhibitors of BGT1, such as the investigational compound EF1502, have demonstrated synergistic anticonvulsant effects when co-administered with GAT1 inhibitors like tiagabine, suggesting a role in modulating neuronal excitability [8, 10]. However, its exact contribution to seizure control remains a subject of ongoing research, as BGT1-deficient models do not always exhibit altered seizure thresholds [8, 14]. Beyond epilepsy, BGT1 is also being investigated for its role in liver failure and other conditions involving osmotic stress [13, 16].

Other names

SLC6A12BGT-1Betaine/GABA transporter 1Na(+)/Cl(-) betaine/GABA transporterGABA transporter 2 (GAT2)GABA transporter 4 (GAT4)

Inhibition of GABA reuptake; modulation of osmolyte transport