Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein
Document Type
Article
Abstract
The efficiency with which N-methyl-D-aspartate receptors (NMDARs) trigger intracellular signaling pathways governs neuronal plasticity, development senescence, and disease. In cultured cortical neurons, suppressing the expression of the NMDAR scaffolding protein PSD-95 (postsynaptic density-95) selectively attenuated excitotoxicity triggered via NMDARs, but not by other glutamate or calcium ion (Ca2+) channels. NMDAR function was unaffected, because receptor expression, NMDA currents, and 45Ca2+ loading were unchanged. Suppressing PSD-95 blocked Ca2+- activated nitric oxide production by NMDARs selectively, without affecting neuronal nitric oxide synthase expression or function. Thus, PSD-95 is required for efficient coupling of NMDAR activity to nitric oxide toxicity, and imparts specificity to excitotoxic Ca2+ signaling.
Publication Date
6-11-1999
Publication Title
Science
ISSN
00368075
Volume
284
Issue
5421
First Page
1845
Last Page
1848
PubMed ID
10364559
Digital Object Identifier (DOI)
10.1126/science.284.5421.1845
Recommended Citation
Sattler, Rita; Xiong, Zhigang; Lu, Wei Yang; Hafner, Mathias; MacDonald, John F.; and Tymianski, Michael, "Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein" (1999). Translational Neuroscience. 1376.
https://scholar.barrowneuro.org/neurobiology/1376