GABA transporter GAT1: a crucial determinant of GABAB receptor activation in cortical circuits?

Advances in Pharmacology
Guillermo González-Burgos

Abstract

The GABA transporter 1 (GAT1), the main plasma membrane GABA transporter in brain tissue, mediates translocation of GABA from the extracellular to the intracellular space. Whereas GAT1-mediated uptake could generally terminate the synaptic effects of GABA, recent studies suggest a more complex physiological role. This chapter reviews evidence suggesting that in hippocampal and neocortical circuits, GAT1-mediated GABA transport regulates the electrophysiological effects of GABA(B) receptor (GABA(B)R) activation by synaptically-released GABA. Contrasting with synaptic GABA(A) receptors, GABA(B)Rs display high GABA binding affinity, slow G protein-coupled mediated signaling, and a predominantly extrasynaptic localization. Such GABA(B)R properties determine production of slow inhibitory postsynaptic potentials (IPSPs) and slow presynaptic effects. Such effects possibly require diffusion of GABA far away from the release sites, and consequently both GABA(B)R-mediated IPSPs and presynaptic effects are strongly enhanced when GAT1-mediated uptake is blocked. Studies are reviewed here which indicate that GABA(B)R-mediated IPSPs seem to be produced by dendrite-targeting GABA neurons including specifically, although perhaps not exclusivel...Continue Reading

Citations

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