Glutamate uptake triggers transporter-mediated GABA release from astrocytes

Héja László

Barabás Péter

Nyitrai Gabriella

Kékesi Adrienna Katalin

Lasztóczi Bálint

Tőke Orsolya

Tárkányi Gábor

Dobolyi Árpád

Palkovits Miklós

Kardos Julianna

MTA TTK/MTA KK/Biomolekuláris Kémiai Intézet (KK 2011-ig!)

MTA TTK/MTA KK/Szerkezeti Kémiai Intézet (KK 2011-ig!)

MTA TKI/MTA-SE Neuromorfológiai és Neuroendokrin Kutatócsoport (2006-ig: MTA-SE Neuroendokrin Kutatócsoport)

MTA TTK/SZKI/Szerves Kémiai Int. jogelőd 2012 előtt

MTA TTK/MFI/MFI jogelőd 2012 előtt

SE/AOK/I/Anatómiai, Szövet- és Fejlődéstani Intézet [2015.12.31]

MTA Természettudományi Kutatóközpont

MTA Támogatott Kutatócsoportok

Semmelweis Egyetem

2014-05-14T05:55:38Z

2014-05-14T05:55:38Z

2009

2014-04-01T10:13:55Z

Background: Glutamate (Glu) and c-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 Ca2+ 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.

Journal Article

pagination=e7153, papers: 12; journalVolume=4; journalIssueNumber=9; journalTitle=PLOS ONE;

http://repo.lib.semmelweis.hu//handle/123456789/80

doi:10.1371/journal.pone.0007153

1265960

000270164600005

19777062

urn:issn:1932-6203