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.