Glial transporters for glutamate, glycine, and GABA: II. GABA transporters.
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 gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Glial cells express the cloned Na(+)/Cl(-)-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.
Instituto de Fisiología Celular, Departamento de Neurociencias, UNAM, México, D.F., México.
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Gadea
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López-Colomé
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009457:Neuroglia / Q000378:metabolism*; D027361:Organic Anion Transporters; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C493413:SLC6A1 protein, human; C493416:SLC6A11 protein, human; C493418:SLC6A13 protein, human; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine