A functional role for both γ-aminobutyric acid (GABA) transporter-1 and GABA transporter-3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus

F. Kersanté,S. Rowley,I. Pavlov,M. Gutierrez-Mecinas,Alexey Semyanov,J. Reul,M. Walker,A. C. Linthorst

Published 2013 in Journal of Physiology

ABSTRACT

•  The extracellular concentration of the neurotransmitter γ‐aminobutyric acid (GABA) is critical in determining GABAA receptor‐mediated tonic conductance in the hippocampus. •  Two GABA transporters (GAT‐1 and GAT‐3) are present in the CA3 and dentate gyrus of the hippocampus. The expression of GAT‐3 is confined to astrocytes and its role in the regulation of GABAergic neurotransmission is unclear. •  Using microdialysis and specific GAT uptake inhibitors we show that not only GAT‐1 but also GAT‐3 contributes to the regulation of hippocampal extracellular concentrations of GABA in rats under in vivo conditions. •  We further found that changes in extracellular concentrations of GABA resulting from both GAT‐1 and GAT‐3 inhibition precipitate supra‐additive changes in tonic conductance in dentate granule cells in vitro. •  These results help us to understand the mechanisms underlying the regulation of GABAergic tonic conductance in the hippocampus and can help to develop improved therapeutic strategies for neurological and psychiatric disorders.

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