title: Different transporter systems regulate extracellular GABA from vesicular and non-vesicular sources.
abstract: Tonic GABA type A (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. In mice, GABA from vesicular sources is regulated by mouse GABA transporter 1 (mGAT1), while that from non-vesicular sources by mouse GABA transporters 3/4 (mGAT3/4). This finding suggests that the two transporter systems do not just provide backup for each other, but regulate distinct signaling pathways. This allows individual tuning of the two signaling systems and indicates that drugs designed to act at specific transporters will have distinct therapeutic actions.
authors.affiliation: RIKEN Brain Science Institute Wako-shi, Saitama, Japan.
authors.forename: Inseon
authors.initials: I
authors.lastname: Song
authors.forename: Kirill
authors.initials: K
authors.lastname: Volynski
authors.forename: Tanja
authors.initials: T
authors.lastname: Brenner
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ushkaryov
authors.forename: Matthew
authors.initials: M
authors.lastname: Walker
authors.forename: Alexey
authors.initials: A
authors.lastname: Semyanov
keywords: GABA; GABA source; GABA transporter; extrasynaptic signaling; interneurons; mutant α-latrotoxin; tonic GABAA conductance