TRANSPORTERS | GABA Transporters: Regulation of Tonic Inhibition

This article reviews the biophysical properties of membrane GABA transporters as they relate to the regulation of extracellular GABA concentrations. Special attention is paid to the dynamic changes in the membrane potential of neurons, and in concentrations of substrate for GABA transporters (GABA, Na+, and Cl−), and the predicted effects these changes would have on GABA transporter function. In particular, we discuss experimental results supporting a role of GABA transporters in the determination of ambient [GABA] in the brain. We conclude that GABA transporters are well suited to maintain ambient [GABA] in the range necessary to maintain tonic inhibition mediated by high-affinity, extrasynaptic GABAA receptors. These extrasynaptic GABAA receptors play an important role in regulating cellular and network excitability.