Nitroxyl anion regulation of the NMDA receptor.
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; Na(2)N(2)O(3)) 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.
Colton
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CA
Division of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA. glia01@aol.com
Gbadegesin
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M
Wink
D A
DA
Miranda
K M
KM
Espey
M G
MG
Vicini
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S
D000975:Antioxidants / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D008564:Membrane Potentials / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D018408:Patch-Clamp Techniques; D004369:Pentetic Acid / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000975:Antioxidants; D002614:Chelating Agents; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D009573:Nitrites; D009589:Nitrogen Oxides; D016194:Receptors, N-Methyl-D-Aspartate; C021229:oxyhyponitrite; D009569:Nitric Oxide; D018698:Glutamic Acid; D004369:Pentetic Acid; C039900:nitroxyl; D005998:Glycine