| NMDA potentiation by visible light in the presence of a fluorescent neurosteroid analogue. | |
| | |
MedLine Citation:
|
PMID: 19403611 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
N-Methyl-D-aspartate (NMDA) receptors are widely studied because of their importance in synaptic plasticity and excitotoxic cell death. Here we report a novel method of potentiating NMDA receptors with fluorescence excited by blue (480 nm) light. In the presence of 300 nM of a (7-nitro-2,1,3-benzoxadiazol-4-yl) amino (NBD)-tagged neuroactive steroid carrier C2-NBD-(3alpha,5alpha)-3-hydroxypregnan-20-one (C2-NBD 3alpha5alphaP), responses of cultured hippocampal neurons to 10 microM NMDA were potentiated to 219.2 +/- 9.2% of the baseline response (100%) by a 30 s exposure to 480 nm light. The potentiation decayed back to baseline with a time constant of 80.6 s. Responses to 1 microM and 100 microM NMDA were potentiated to 147.9 +/- 9.6% and 174.1 +/- 15.6% of baseline, respectively, suggesting that visible-light potentiation is relatively insensitive to NMDA concentration. Peak autaptic NMDA responses were potentiated to 178.9 +/- 22.4% of baseline. Similar potentiation was seen with 10 microM NBD-lysine, suggesting that visible-light potentiation is not a steroid effect. Potentiation was also seen with a steroid analogue in which the NBD was replaced with fluorescein, suggesting that NBD is not the only fluorophore capable of supporting visible-light potentiation. UV light and redox potentiation of NMDA receptors largely occluded subsequent blue light potentiation (127.7 +/- 7.4% and 120.2 +/- 6.2% of baseline, respectively). The NR1a(C744A,C798A) mutant that is insensitive to redox and UV potentiation was also largely unaffected by visible-light potentiation (135.0 +/- 10.0% of baseline). Finally, we found that the singlet oxygen scavenger furfuryl alcohol decreased visible-light potentiation. Collectively, these data suggest that visible-light potentiation of NMDA receptors by fluorescence excitation shares mechanisms with UV and redox potentiation and may involve singlet oxygen production. |
| | |
Authors:
|
Lawrence N Eisenman; Hong-Jin Shu; Cunde Wang; Elias Aizenman; Douglas F Covey; Charles F Zorumski; Steven Mennerick |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-04-29 |
Journal Detail:
|
Title: The Journal of physiology Volume: 587 ISSN: 1469-7793 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 2009 Jun |
Date Detail:
|
Created Date: 2009-06-15 Completed Date: 2009-09-21 Revised Date: 2010-09-27 |
Medline Journal Info:
|
Nlm Unique ID: 0266262 Medline TA: J Physiol Country: England |
Other Details:
|
Languages: eng Pagination: 2937-47 Citation Subset: IM |
Affiliation:
|
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, Box 8111, St Louis, MO 63110, USA. leisenman@wustl.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cells, Cultured Electrophysiology Fluorescent Dyes* Free Radical Scavengers / pharmacology Furans / pharmacology Hippocampus / chemistry, physiology Light* Oxadiazoles* Oxidation-Reduction Patch-Clamp Techniques Pregnanolone / analogs & derivatives* Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Receptors, GABA-A / drug effects Receptors, N-Methyl-D-Aspartate / drug effects, physiology*, radiation effects* Ultraviolet Rays |
| Grant Support | |
ID/Acronym/Agency:
|
AA12952/AA/NIAAA NIH HHS; GM 47969/GM/NIGMS NIH HHS; MH77791/MH/NIMH NIH HHS; MH78823/MH/NIMH NIH HHS; NS44041/NS/NINDS NIH HHS; NS54174/NS/NINDS NIH HHS; P30NS057105/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Fluorescent Dyes; 0/Free Radical Scavengers; 0/Furans; 0/Oxadiazoles; 0/Reactive Oxygen Species; 0/Receptors, GABA-A; 0/Receptors, N-Methyl-D-Aspartate; 128-20-1/Pregnanolone; 98-00-0/furfuryl alcohol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mast cell-cholinergic nerve interaction in mouse airways.
Next Document: Altered firing pattern of single-unit muscle sympathetic nerve activity during handgrip exercise in ...