Nitroxyl anion regulation of the NMDA receptor

Citation
Ca. Colton et al., Nitroxyl anion regulation of the NMDA receptor, J NEUROCHEM, 78(5), 2001, pp. 1126-1134
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
78
Issue
5
Year of publication
2001
Pages
1126 - 1134
Database
ISI
SICI code
0022-3042(200109)78:5<1126:NAROTN>2.0.ZU;2-A
Abstract
Nitric oxide (NO) is an important regulator of NMDA channel function in the CNS. Recent findings suggest that nitroxyl anion (NO-) may also be generat ed by nitric oxide synthase, which catalyzes production of NO. Using recomb inant NMDA receptors (NMDA-r) transfected into human embryonic kidney cells , our data demonstrate that the nitroxyl anion donor, Angeli's salt (AS; Na 2N2O3) dramatically blocked glycine-independent desensitization in NMDA-r c ontaining NR1-NR2A subunits. AS did not affect glycine-dependent desensitiz ation, calcium dependent inactivation or glutamate affinity for the NMDA-r. This effect could be mimicked by treatment with DPTA, a metal chelator and was not evident under hypoxic conditions. In contrast, receptors containin g the NR1-NR2B subunits demonstrated an approximate 25% reduction in whole cell currents in the presence of AS with no apparent change in desensitizat ion. Our data suggest that the regulation of NMDA-r function by nitroxyl an ion is distinctly different from NO and may result in different cellular ou tcomes compared with NO.