Madry, Christian ; Betz, Heinrich ; Geiger, Jörg R. P. ; Laube, Bodo (2008)
Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist.
In: Proceedings of the National Academy of Sciences of the United States of America, 105 (34)
Article, Bibliographie
Abstract
Coassembly of the glycine-binding NMDA receptor subunits NR1 and NR3A results in excitatory glycine receptors of low efficacy. Here, we report that micromolar concentrations of the divalent cation Zn(2+) produce a 10-fold potentiation of NR1/NR3A receptor responses, which resembles that seen upon antagonizing glycine binding to the NR1 subunit. Coapplication of both Zn(2+) and NR1 antagonist caused a supralinear potentiation, resulting in a >120-fold increase of glycine-activated currents. At concentrations >50 microM, Zn(2+) alone generated receptor currents with similar efficacy as glycine, implying that NR1/NR3A receptors can be activated by different agonists. Point mutations in the NR1 and NR3A glycine-binding sites revealed that both the potentiating and agonistic effects of Zn(2+) are mediated by the ligand-binding domain of the NR1 subunit. In conclusion, Zn(2+) acts as a potent positive modulator and agonist at the NR1 subunit of NR1/NR3A receptors. Our results suggest that this unconventional member of the NMDA receptor family may in vivo be gated by the combined action of glycine and Zn(2+) or a yet unknown second ligand.
| Item Type: | Article |
|---|---|
| Erschienen: | 2008 |
| Creators: | Madry, Christian ; Betz, Heinrich ; Geiger, Jörg R. P. ; Laube, Bodo |
| Type of entry: | Bibliographie |
| Title: | Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist. |
| Language: | English |
| Date: | 2008 |
| Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume of the journal: | 105 |
| Issue Number: | 34 |
| Abstract: | Coassembly of the glycine-binding NMDA receptor subunits NR1 and NR3A results in excitatory glycine receptors of low efficacy. Here, we report that micromolar concentrations of the divalent cation Zn(2+) produce a 10-fold potentiation of NR1/NR3A receptor responses, which resembles that seen upon antagonizing glycine binding to the NR1 subunit. Coapplication of both Zn(2+) and NR1 antagonist caused a supralinear potentiation, resulting in a >120-fold increase of glycine-activated currents. At concentrations >50 microM, Zn(2+) alone generated receptor currents with similar efficacy as glycine, implying that NR1/NR3A receptors can be activated by different agonists. Point mutations in the NR1 and NR3A glycine-binding sites revealed that both the potentiating and agonistic effects of Zn(2+) are mediated by the ligand-binding domain of the NR1 subunit. In conclusion, Zn(2+) acts as a potent positive modulator and agonist at the NR1 subunit of NR1/NR3A receptors. Our results suggest that this unconventional member of the NMDA receptor family may in vivo be gated by the combined action of glycine and Zn(2+) or a yet unknown second ligand. |
| Divisions: | 10 Department of Biology 10 Department of Biology > Neurophysiology and Neurosensory Systems ?? fb10_zoologie ?? |
| Date Deposited: | 11 Apr 2011 09:19 |
| Last Modified: | 05 Mar 2019 06:48 |
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