Excitotoxic superoxide production and neuronal death require both ionotropic and non-ionotropic NMDA receptor signaling.

ABSTRACT: NMDA-type glutamate receptors (NMDAR) trigger superoxide production by neuronal NADPH oxidase-2 (NOX2), which if sustained leads to cell death. This process involves Ca²⁺ influx through NMDAR channels. By contrast, comparable Ca²⁺ influx by other routes does not induce NOX2 activation or cell death. This contrast has been attributed to site-specific effects of Ca²⁺ flux through NMDAR. Here we show instead that it stems from non-ionotropic signaling by NMDAR GluN2B subunits. To evaluate non-ionotropic effects, mouse cortical neurons were treated with NMDA together with 7-chlorokynurenate, L-689,560, or MK-801, which block Ca²⁺ influx through NMDAR channels but not NMDA binding. NMDA-induced superoxide formation was prevented by the channel blocker

SUBMITTER: Minnella AM 

PROVIDER: S-EPMC6269523 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature