Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 277: C673-C683, 1999;
0363-6143/99 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gbadegesin, M.
Right arrow Articles by Colton, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gbadegesin, M.
Right arrow Articles by Colton, C. A.
Vol. 277, Issue 4, C673-C683, October 1999

Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death

Muyiwa Gbadegesin1, Stefano Vicini1,2, Sandra J. Hewett3, David A. Wink4, Michael Espey4, Ryszard M. Pluta5, and Carol A. Colton1,2

1 Interdisciplinary Program in Neuroscience and 2 Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia 20007; 3 Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut 06030; and 4 Radiation Biology, National Cancer Institute, and 5 Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892

Nitric oxide (NO) released from a new chemical class of donors enhances N-methyl-D-aspartate (NMDA) channel activity. Using whole cell and single-channel patch-clamp techniques, we have shown that (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]-NO (PAPA-NO) and diethylamine NO, commonly termed NONOates, potentiate the glutamate-mediated response of recombinant rat NMDA receptors (NR1/NR2A) expressed in HEK-293 cells. The overall effect is an increase in both peak and steady-state whole cell currents induced by glutamate. Single-channel studies demonstrate a significant increase in open probability but no change in the mean single-channel open time or mean channel conductance. Reduction in oxygen levels increased and prolonged the PAPA-NO-induced change in both peak and steady-state glutamate currents in transfected HEK cells. PAPA-NO also enhanced cell death in primary cultures of rodent cortical neurons deprived of oxygen and glucose. This potentiation of neuronal injury was blocked by MK-801, indicating a critical involvement of NMDA receptor activation. The NO-induced increase in NMDA channel activity as well as NMDA receptor-mediated cell death provide firm evidence that NO modulates the NMDA channel in a manner consistent with both a physiological role under normoxic conditions and a pathophysiological role under hypoxic conditions.

N-methyl-D-aspartate; oxygen-glucose deprivation; PAPA-NO


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. A. Wink, K. M. Miranda, T. Katori, D. Mancardi, D. D. Thomas, L. Ridnour, M. G. Espey, M. Feelisch, C. A. Colton, J. M. Fukuto, et al.
Orthogonal properties of the redox siblings nitroxyl and nitric oxide in the cardiovascular system: a novel redox paradigm
Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2264 - H2276.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
M. Renganathan, T. R. Cummins, and S. G. Waxman
Nitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation
J Neurophysiol, February 1, 2002; 87(2): 761 - 775.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. G. Espey, K. M. Miranda, D. D. Thomas, and D. A. Wink
Distinction between Nitrosating Mechanisms within Human Cells and Aqueous Solution
J. Biol. Chem., August 3, 2001; 276(32): 30085 - 30091.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online