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GAT

GABA is the major inhibitory neurotransmitter in the brain and GABA re-uptake transport is one of the several pathways in the complex regulation of GABA activity. The first GABA transporter was GAT-1. The rat GAT, human GAT and mouse GAT are highly homologous (= 97%) proteins consisting of 599 amino acids. The proteins are termed rGAT-1, hGAT-1 and mGAT-1 respectively. Two other GABA transporters from rat brain related to GAT-1 but with distinct homology and pharmacological properties have been cloned, expressed in mammalian cells and named GAT-2 and GAT-3 respectively. Transporters function as molecularshuttles, transferring substrates across the membrane one moleculeat a time,then going back for more. GABA transporters belong to the family of Na+- and Cl-- coupled transporters, so named because these ions are co-transported with substrate. GABA transporters play a fundamental role in regulating extrasynaptic GABA levels, with inhibition of astroglial transporters being a critical target with anticonvulsant potential.

References

1.Soudijn W, et al. Curr Med Chem. 2000;7(10):1063–1079.
2.Borden LA. Neurochem Int. 1996;29(4):335–356.
3.Schousboe A, et al. Neurochem Res. 2014;39(10):1980–1987.

Membrane Transporter/Ion Channel

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