GABA is a major inhibitory neurotransmitter and the GABAergic transmission is terminated by the rapid Na+/Cl-dependent uptake of through GABA transporters. It has been subdivided into neural and glial uptake systems on the basis of pharmacological properties. Recently, molecular cloning studies have identified multiple subtypes of GABA transporters (GAT1, GAT2, GAT3; and betaine GABA transporter (BGT-1). There is ~50% homology between various GABA transporter subtypes. GABA transporters are predicted to contain 12 potential transmembrane domains. The NH2 and COOHtermini are predicted to be intracellular. Two of the high affinity (Km~10 uM) rat GABA transporters (GAT2 and GAT3/GAT-B) share higher amino acid identity (68% and 65%, respectively) with the kidney betaine transporter than with GAT-1 (52% AA identity). GAT1and GAT3 have been detected in various parts of the brain while GAT2 is found in many tissues. It appears that GAT1 and GAT3 are involved in distinct GABAergic transmission while GAT2 may be important in non-neural functions.
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