Role of Na,K-ATPase alpha 1 and alpha 2 Isoforms in the Support of Astrocyte Glutamate Uptake
2014 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 6, e98469- p.Article in journal (Refereed) Published
Glutamate released during neuronal activity is cleared from the synaptic space via the astrocytic glutamate/Na+ co-transporters. This transport is driven by the transmembrane Na+ gradient mediated by Na,K-ATPase. Astrocytes express two isoforms of the catalytic Na, K-ATPase alpha subunits; the ubiquitously expressed alpha 1 subunit and the alpha 2 subunit that has a more specific expression profile. In the brain alpha 2 is predominantly expressed in astrocytes. The isoforms differ with regard to Na+ affinity, which is lower for alpha 2. The relative roles of the alpha 1 and alpha 2 isoforms in astrocytes are not well understood. Here we present evidence that the presence of the alpha 2 isoform may contribute to a more efficient restoration of glutamate triggered increases in intracellular sodium concentration [Na+](i). Studies were performed on primary astrocytes derived from E17 rat striatum expressing Na, K-ATPase alpha 1 and alpha 2 and the glutamate/Na+ co-transporter GLAST. Selective inhibition of alpha 2 resulted in a modest increase of [Na+](i) accompanied by a disproportionately large decrease in uptake of aspartate, an indicator of glutamate uptake. To compare the capacity of alpha 1 and alpha 2 to handle increases in [Na+](i) triggered by glutamate, primary astrocytes overexpressing either alpha 1 or alpha 2 were used. Exposure to glutamate 200 mM caused a significantly larger increase in [Na+](i) in alpha 1 than in alpha 2 overexpressing cells, and as a consequence restoration of [Na+](i), after glutamate exposure was discontinued, took longer time in alpha 1 than in alpha 2 overexpressing cells. Both alpha 1 and alpha 2 interacted with astrocyte glutamate/Na+ co-transporters via the 1st intracellular loop.
Place, publisher, year, edition, pages
2014. Vol. 9, no 6, e98469- p.
Other Medical Sciences
IdentifiersURN: urn:nbn:se:kth:diva-147724DOI: 10.1371/journal.pone.0098469ISI: 000336841400033ScopusID: 2-s2.0-84902449239OAI: oai:DiVA.org:kth-147724DiVA: diva2:732926
QC 201407072014-07-072014-07-032014-07-07Bibliographically approved