GABA transporters in the mammalian cerebral cortex: Localization, development and pathological implications

  • Conti F
  • Minelli A
  • Melone M
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Abstract

The extracellular levels of γ-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. © 2004 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Amino acid neurotransmitters
  • D
  • GABA
  • Glia
  • Inhibitory synapses
  • Neurons
  • Neurotransmitter uptake

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Authors

  • Fiorenzo Conti

  • Andrea Minelli

  • Marcello Melone

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