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| Content Provider | PubMed Central |
|---|---|
| Author | Kersanté, Flavie Rowley, Samuel C. S. Pavlov, Ivan María, Gutièrrez-mecinas Semyanov, Alexey Reul, Johannes M. H. M. Walker, Matthew C. Linthorst, Astrid C. E. |
| Copyright Year | 2013 |
| Abstract | Tonic γ-aminobutyric acid (GABA)A receptor-mediated signalling controls neuronal network excitability in the hippocampus. Although the extracellular concentration of GABA (e[GABA]) is critical in determining tonic conductances, knowledge on how e[GABA] is regulated by different GABA transporters (GATs) in vivo is limited. Therefore, we studied the role of GATs in the regulation of hippocampal e[GABA] using in vivo microdialysis in freely moving rats. Here we show that GAT-1, which is predominantly presynaptically located, is the major GABA transporter under baseline, quiescent conditions. Furthermore, a significant contribution of GAT-3 in regulating e[GABA] was revealed by administration of the GAT-3 inhibitor SNAP-5114 during simultaneous blockade of GAT-1 by NNC-711. Thus, the GABA transporting activity of GAT-3 (the expression of which is confined to astrocytes) is apparent under conditions in which GAT-1 is blocked. However, sustained neuronal activation by K+-induced depolarization caused a profound spillover of GABA into the extrasynaptic space and this increase in e[GABA] was significantly potentiated by sole blockade of GAT-3 (i.e. even when uptake of GAT-1 is intact). Furthermore, experiments using tetrodotoxin to block action potentials revealed that GAT-3 regulates extrasynaptic GABA levels from action potential-independent sources when GAT-1 is blocked. Importantly, changes in e[GABA] resulting from both GAT-1 and GAT-3 inhibition directly precipitate changes in tonic conductances in dentate granule cells as measured by whole-cell patch-clamp recording. Thus, astrocytic GAT-3 contributes to the regulation of e[GABA] in the hippocampus in vivo and may play an important role in controlling the excitability of hippocampal cells when network activity is increased. |
| Related Links | http://dx.doi.org/10.1113/jphysiol.2012.246298 |
| Ending Page | 2441 |
| Page Count | 13 |
| Starting Page | 2429 |
| File Format | |
| ISSN | 00223751 |
| e-ISSN | 14697793 |
| Journal | The Journal of Physiology |
| Issue Number | Pt 10 |
| Volume Number | 591 |
| Language | English |
| Publisher | Blackwell Science Inc |
| Publisher Date | 2013-05-01 |
| Access Restriction | Open |
| Rights Holder | Blackwell Science Inc |
| Subject Keyword | Physiology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
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