Glutamate uptake triggers transporter-mediated GABA release from astrocytes. Export

@article{citeulike:5839246, abstract = {BACKGROUND: Glutamate (Glu) and gamma-aminobutyric acid (GABA) transporters play important roles in regulating neuronal activity. Glu is removed from the extracellular space dominantly by glial transporters. In contrast, GABA is mainly taken up by neurons. However, the glial GABA transporter subtypes share their localization with the Glu transporters and their expression is confined to the same subpopulation of astrocytes, raising the possibility of cooperation between Glu and GABA transport processes. METHODOLOGY/PRINCIPAL FINDINGS: Here we used diverse biological models both in vitro and in vivo to explore the interplay between these processes. We found that removal of Glu by astrocytic transporters triggers an elevation in the extracellular level of GABA. This coupling between excitatory and inhibitory signaling was found to be independent of Glu receptor-mediated depolarization, external presence of Ca(2+) and glutamate decarboxylase activity. It was abolished in the presence of non-transportable blockers of glial Glu or GABA transporters, suggesting that the concerted action of these transporters underlies the process. CONCLUSIONS/SIGNIFICANCE: Our results suggest that activation of Glu transporters results in GABA release through reversal of glial GABA transporters. This transporter-mediated interplay represents a direct link between inhibitory and excitatory neurotransmission and may function as a negative feedback combating intense excitation in pathological conditions such as epilepsy or ischemia.}, author = {H\'{e}ja, L\'{a}szl\'{o} and Barab\'{a}s, P\'{e}ter and Nyitrai, Gabriella and K\'{e}kesi, Katalin A. and Laszt\'{o}czi, B\'{a}lint and Toke, Orsolya and T\'{a}rk\'{a}nyi, G\'{a}bor and Madsen, Karsten and Schousboe, Arne and Dobolyi, Arp\'{a}d and Palkovits, Mikl\'{o}s and Kardos, Julianna}, citeulike-article-id = {5839246}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0007153}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19777062}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19777062}, day = {24}, doi = {10.1371/journal.pone.0007153}, issn = {1932-6203}, journal = {PloS one}, keywords = {epilepsy, gaba, glu, glutamate, tonic\_inhibition, transporter}, month = {September}, number = {9}, pages = {e7153+}, posted-at = {2009-09-25 09:37:52}, priority = {0}, publisher = {Public Library of Science}, title = {Glutamate uptake triggers transporter-mediated GABA release from astrocytes.}, url = {http://dx.doi.org/10.1371/journal.pone.0007153}, volume = {4}, year = {2009} }

TY - JOUR ID - citeulike:5839246 L3 - citeulike-article-id:5839246 N2 - BACKGROUND: Glutamate (Glu) and gamma-aminobutyric acid (GABA) transporters play important roles in regulating neuronal activity. Glu is removed from the extracellular space dominantly by glial transporters. In contrast, GABA is mainly taken up by neurons. However, the glial GABA transporter subtypes share their localization with the Glu transporters and their expression is confined to the same subpopulation of astrocytes, raising the possibility of cooperation between Glu and GABA transport processes. METHODOLOGY/PRINCIPAL FINDINGS: Here we used diverse biological models both in vitro and in vivo to explore the interplay between these processes. We found that removal of Glu by astrocytic transporters triggers an elevation in the extracellular level of GABA. This coupling between excitatory and inhibitory signaling was found to be independent of Glu receptor-mediated depolarization, external presence of Ca(2+) and glutamate decarboxylase activity. It was abolished in the presence of non-transportable blockers of glial Glu or GABA transporters, suggesting that the concerted action of these transporters underlies the process. CONCLUSIONS/SIGNIFICANCE: Our results suggest that activation of Glu transporters results in GABA release through reversal of glial GABA transporters. This transporter-mediated interplay represents a direct link between inhibitory and excitatory neurotransmission and may function as a negative feedback combating intense excitation in pathological conditions such as epilepsy or ischemia. IS - 9 JF - PloS one SN - 1932-6203 TI - Glutamate uptake triggers transporter-mediated GABA release from astrocytes. PB - Public Library of Science VL - 4 SP - e7153 KW - epilepsy KW - gaba KW - glu KW - glutamate KW - tonic_inhibition KW - transporter AU - Héja, László AU - Barabás, Péter AU - Nyitrai, Gabriella AU - Kékesi, Katalin AU - Lasztóczi, Bálint AU - Toke, Orsolya AU - Tárkányi, Gábor AU - Madsen, Karsten AU - Schousboe, Arne AU - Dobolyi, Arpád AU - Palkovits, Miklós AU - Kardos, Julianna PY - 2009/09/24/ UR - http://dx.doi.org/10.1371/journal.pone.0007153 ER -