Referenced in: none

Automatically associated channels: Kv10.1

Title: Oxidative glutamate toxicity can be a component of the excitotoxicity cascade.

Authors: D Schubert, D Piasecki

Journal, date & volume: J. Neurosci., 2001 Oct 1 , 21, 7455-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11567035

Abstract
Along with ionotropic and metabotropic glutamate receptors, the cystine/glutamate antiporter x(c)(-) may play a critical role in CNS pathology. High levels of extracellular glutamate inhibit the import of cystine, resulting in the depletion of glutathione and a form of cell injury called oxidative glutamate toxicity. Here we show that a portion of the cell death associated with NMDA receptor-initiated excitotoxicity can be caused by oxidative glutamate toxicity. In primary mouse cortical neurons the cell death resulting from the short-term application of 10 microm glutamate can be divided into NMDA and NMDA receptor-independent phases. The NMDA receptor-independent component is associated with high extracellular glutamate and is inhibited by a variety of reagents that block oxidative glutamate toxicity. These results suggest that oxidative glutamate toxicity toward neurons lacking functional NMDA receptors can be a component of the excitotoxicity-initiated cell death pathway.