Glial transporters for glutamate, glycine, and GABA: II. GABA transporters

Abstract

The termination of chemical neurotransmission in the central nervous system (CNS) involves the rapid removal of neurotransmitter from synapses. This is fulfilled by specific transport systems in neurons and glia, including those for ␥-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Glial cells express the cloned Na ϩ /Cl Ϫ -dependent, high-affinity GABA transporters (GATs) GAT1, GAT2, and GAT3, as well as the low-affinity transporter BGT1. In situ hybridization and immunocytochemistry have revealed that each transporter shows distinct regional distribution in the brain and the retina. The neuronal vs. glial localization of the different transporters is not clear-cut, and variations according to species, neighboring excitatory synapses, and developmental stage have been reported. The localization, stoichiometry, and regulation of glial GATs are outlined, and the participation of these structures in development, osmoregulation, and neuroprotection are discussed. A decrease in GABAergic neurotransmission has been implicated in the pathophysiology of several CNS disorders, particularly in epilepsy. Since drugs which selectively inhibit glial but not neuronal GABA uptake exert anticonvulsant activity, clearly the establishment of the molecular mechanisms controlling GATs in glial cells will be an aid in the chemical treatment of several CNS-related diseases.

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

“…Epilepsy. GABA transporter inhibitors are in general anticonvulsants and have shown therapeutic potential as antiepileptic agents (Dalby, 2000;Czuczwar and Patsalos, 2001; Dalby and Mody, 2001; Gadea and López-Colomé, 2001;Schousboe et al, 2004;Meldrum and Rogawski, 2007). Covering a wide range of neurological disorders characterized by recurrent seizure episodes, epilepsy is caused by abnormally excessive excitatory activity.…”

Developmental expression of GABA transporter-1 and 3 during formation of the GABAergic synapses in the mouse cerebellar cortex

“…GATs mediate the GABA-uptake from the synaptic cleft by exchanging Na + and Cl -ions in the mature brain [5,10,17] . Molecular cloning has isolated four GATs: GAT-1, GAT-2, GAT-3 and BGT-1.…”

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

“…Most of the interest in these transporters has been in relation to their roles in the inactivation of GABA signaling in the central nervous system (3)(4)(5). (Here, we use the GABA transporter nomenclature adopted by the HUGO Gene Nomenclature Committee.)…”