Seizure activity results in increased tyrosine phosphorylation of the N-methyl-D-aspartate receptor in the hippocampus

Systemic administration of kainic acid (KA) induces. status epilepticus (SE ) that causes neurodegeneration and may subsequently lead to spontaneous re current seizures. We investigated the effects of KA-induced SE on tyrosine phosphorylation and solubility properties of the NMDA receptor. Following 1 h of SE, total protein tyrosine phosphorylation was elevated in both the h ippocampus and frontal cortex relative to controls. Tyrosine phosphorylatio n of the NMDA receptor subunits NR2A and NR2B was also enhanced following S E. Animals that received KA but did not develop SE, did not exhibit increas ed tyrosine phosphorylation. SE resulted in a decrease in the solubility of NMDA receptor subunits and of PSD-95 in 1% deoxycholate. In contrast, the detergent solubility of AMPA and kainate receptors was not affected. These findings demonstrate that SE alters tyrosine phosphorylation of the NMDA re ceptor, and indicate that the interaction of the NMDA receptor with other c omponents of the NMDA receptor complex are altered as. a consequence of sei zure activity. (C) 2001 Elsevier Science B V. All rights reserved.