AUTHOR=Song Inseon , Volynski Kirill , Brenner Tanja , Ushkaryov Yuri , Walker Matthew , Semyanov Alexey 

TITLE=Different transporter systems regulate extracellular GABA from vesicular and non-vesicular sources

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 7 - 2013

YEAR=2013

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2013.00023

DOI=10.3389/fncel.2013.00023

ISSN=1662-5102

ABSTRACT=Tonic GABAA conductance is a key factor regulating neuronal excitability and computation in neuronal networks. The magnitude of the tonic GABAA conductance depends on the concentration of ambient GABA originating from vesicular and non-vesicular sources and is tightly regulated by GABA uptake. Here we show that the transport system regulating ambient GABA responsible for tonic GABAA conductances in hippocampal CA1 interneurons depends on its source. GABA from vesicular sources is regulated by GABA transporter GAT1, while that from non-vesicular sources by transporter GAT3/4. This finding suggests that two transporter systems do not just provide backup to each other, but regulate distinct signaling pathways. This allows individual tuning of two signaling systems and indicates that drugs designed to act at specific transporters will have distinct therapeutic actions.