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 generated by nitric oxide synthase, which catalyzes production of NO. Using recombinant NMDA receptors (NMDA-r) transfected into human embryonic kidney cells, our data demonstrate that the nitroxyl anion donor, Angeli's salt (AS; Na2N2O3) dramatically blocked glycine-independent desensitization in NMDA-r containing NR1-NR2A subunits. AS did not affect glycine-dependent desensitization, 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 containing the NR1-NR2B subunits demonstrated an approximate 25% reduction in whole cell currents in the presence of AS with no apparent change in desensitization. Our data suggest that the regulation of NMDA-r function by nitroxyl anion is distinctly different from NO and may result in different cellular outcomes compared with NO.
Original language | English (US) |
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Pages (from-to) | 1126-1134 |
Number of pages | 9 |
Journal | Journal of neurochemistry |
Volume | 78 |
Issue number | 5 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Angeli's salt
- Glycine independent desensitization
- Hypoxia
- N-methyl-D-aspartate
- Nitroxyl anion
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience