| First Author | Matos M | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 47 | Pages | 18492-502 |
| PubMed ID | 24259572 | Mgi Jnum | J:204161 |
| Mgi Id | MGI:5529735 | Doi | 10.1523/JNEUROSCI.1828-13.2013 |
| Citation | Matos M, et al. (2013) Antagonistic interaction between adenosine A2A receptors and Na+/K+-ATPase-alpha2 controlling glutamate uptake in astrocytes. J Neurosci 33(47):18492-502 |
| abstractText | Astrocytic glutamate transporter-1 (GLT-I) is critical to control the bulk of glutamate uptake and, thus, to regulate synaptic plasticity and excitotoxicity. GLT-I glutamate uptake is driven by the sodium gradient implemented by Na(+)/K(+)-ATPases (NKAs) and the alpha2 subunit of NKA (NKA-alpha2) is actually linked to GLT-I to regulate astrocytic glutamate transport. We recently found that adenosine A2A receptors (A2ARs), which control synaptic plasticity and neurodegeneration, regulate glutamate uptake through unknown mechanisms. Here we report that A2AR activation decreases NKA activity selectively in astrocytes to inhibit glutamate uptake. Furthermore, we found a physical association of A2ARs with NKA-alpha2s in astrocytes, as gauged by coimmunoprecipitation and in situ proximity ligation assays, in the cerebral cortex and striatum, two brain regions where A2ARs inhibit the astrocytic glutamate uptake. Moreover, the selective deletion of A2ARs in astrocytes (using Gfa2-A2AR-KO mice) leads to a concurrent increase of both astrocytic glutamate uptake and NKA-alpha2 levels and activity in the striatum and cortex. This coupling of astrocytic A2ARs to the regulation of glutamate transport through modulation of NKA-alpha2 activity provides a novel mechanism linking neuronal activity to ion homeostasis controlling glutamatergic activity, all of which are processes intricately associated with the etiology of several brain diseases. |
