Co-Existence of GABA and Glu Transporters in the Central Nervous System

Giambattista      Bonanno; Luca      Raiteri; Silvio      Paluzzi; Simona      Zappettini; Cesare      Usai; Maurizio      Raiteri

doi:10.2174/156802606777323746

Abstract

Co-localization of transporters able to recapture the released or endogenously synthesized transmitter (homotransporters) and of transporters that can selectively take up transmitters/modulators originating from neighbouring structures (heterotransporters) has been demonstrated to occur within the same axon terminal of several neuronal phenotypes. Activation of terminal heterotransporters invariably leads to the release of the transmitter specific to the terminal. Heterotransporters are also increasingly reported to exist on neuronal soma/dendrites and nerve terminals, on the basis of morphological experiments. The functions of somatodendritic heterotransporters has been investigated only in a very limited number of cases. Release-regulating GABA heterotransporters of the GAT-1 type exist on Glu nerve terminals in different rodent brain regions including spinal cord. Activation of GABA heterotransporters provokes release of Glu, which takes place by reversal of the Glu homotransporter and by anion channel opening. Interestingly, the release of Glu induced by GABA in spinal cord is dramatically enhanced in a transgenic mouse model of amyotrophic lateral sclerosis and this effect seems to represent the most precocious mechanism that increases extracellular Glu concentration, reported to occur in the pathomechanism.

Keywords: Concept of heterotransporters, reciprocal modulation of GABA and Glu release, GAT-1 heterotransporter, anion channel opening, reversal of EAAT-2, amyotrophic lateral sclerosis

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