Song, I;
Volynski, K;
Brenner, T;
Ushkaryov, Y;
Walker, M;
Semyanov, A;
(2013)
Different transporter systems regulate extracellular GABA from vesicular and non-vesicular sources.
Front Cell Neurosci
, 7
, Article 23. 10.3389/fncel.2013.00023.
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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.
| Type: | Article |
|---|---|
| Title: | Different transporter systems regulate extracellular GABA from vesicular and non-vesicular sources. |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fncel.2013.00023 |
| Publisher version: | http://dx.doi.org/10.3389/fncel.2013.00023 |
| Language: | English |
| Additional information: | © 2013 Song, Volynski, Brenner, Ushkaryov, Walkerand Semyanov. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. PMCID: PMC3595500 |
| Keywords: | GABA, GABA source, GABA transporter, extrasynaptic signaling, interneurons, mutant α-latrotoxin, tonic GABAA conductance |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1388411 |
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