GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications.
The extracellular levels of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian cerebral cortex, are regulated by specific high-affinity, Na+/Cl- dependent transporters. Four distinct genes encoding GABA transporters (GATs), named GAT-1, GAT-2, GAT-3, and BGT-1 have been identified using molecular cloning. Of these, GAT-1 and -3 are expressed in the cerebral cortex. Studies of the cortical distribution, cellular localization, ontogeny and relationships of GATs with GABA-releasing elements using a variety of light and electron microscopic immunocytochemical techniques have shown that: (i) a fraction of GATs is strategically placed to mediate GABA uptake at fast inhibitory synapses, terminating GABA's action and shaping inhibitory postsynaptic responses; (ii) another fraction may participate in functions such as the regulation of GABA's diffusion to neighboring synapses and of GABA levels in cerebrospinal fluid; (iii) GATs may play a role in the complex processes regulating cortical maturation; and (iv) GATs may contribute to the dysregulation of neuronal excitability that accompanies at least two major human diseases: epilepsy and ischemia.
Conti
Fiorenzo
F
Dipartimento di Neuroscienze, Sezione di Fisiologia, Università Politecnica delle Marche, Via Tronto 10/A, Torrette di Ancona, I-60020 Ancona, Italy. f.conti@univpm.it
Minelli
Andrea
A
Melone
Marcello
M
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D004827:Epilepsy / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009422:Nervous System Diseases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C493413:SLC6A1 protein, human; C493416:SLC6A11 protein, human; C493418:SLC6A13 protein, human; D005680:gamma-Aminobutyric Acid