title: Redox sites of NMDA receptors can modulate epileptiform activity in hippocampal slices from kainic acid-treated rats.
abstract: Using an animal model of temporal lobe epilepsy, the kainic acid lesioned rat hippocampus, we have evaluated the possibility of modulating glutamate N-methyl-D-aspartate (NMDA) receptor-dependent evoked epileptiform activity through the manipulation of NMDA receptor redox sites. Epileptiform activity was recorded extracellularly from hippocampal slices, in the stratum pyramidale of the CA1 area, and the effects of the oxidizing reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and the reducing agent Tris(2-carboxy ethyl)phosphine (TCEP) on these responses were quantified. Epileptiform activity was substantially reduced in the presence of DTNB but was fully reinstated with the application of TCEP. The effects of both drugs persisted even after wash. Epileptiform activity was totally abolished in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid. These results suggest that epileptiform activity can be controlled by manipulation of the redox sites of NMDA receptors and raise the possibility of developing new anticonvulsant drugs which do not fully block NMDA receptor-mediated synaptic transmission.
authors.affiliation: Instituto de Fisiología Cellular, UNAM, México, D.F., Mexico.
authors.forename: O
authors.initials: O
authors.lastname: Quesada
authors.forename: J
authors.initials: J
authors.lastname: Hirsch
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: C
authors.initials: C
authors.lastname: Bernard
mesh_terms: D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy; D006624:Hippocampus / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D010084:Oxidation-Reduction; D010720:Phosphines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007608:Kainic Acid; D010720:Phosphines; D016194:Receptors, N-Methyl-D-Aspartate; C080938:tris(2-carboxyethyl)phosphine