title: Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus.
abstract: After 1h of lithium-pilocarpine status epilepticus (SE), immunocytochemical labeling of NMDA receptor NR1 subunits reveals relocation of subunits from the interior to the cell surface of dentate gyrus granule cells and CA3 pyramidal cells. Simultaneously, an increase in NMDA-miniature excitatory postsynaptic currents (mEPSC) as well as an increase in NMDA receptor-mediated tonic currents is observed in hippocampal slices after SE. Mean-variance analysis of NMDA-mEPSCs estimates that the number of functional postsynaptic NMDA receptors per synapse increases 38% during SE, and antagonism by ifenprodil suggests that an increase in the surface representation of NR2B-containing NMDA receptors is responsible for the augmentation of both the phasic and tonic excitatory currents with SE. These results provide a potential mechanism for an enhancement of glutamatergic excitation that maintains SE and may contribute to excitotoxic injury during SE. Therapies that directly antagonize NMDA receptors may be a useful therapeutic strategy during refractory SE.
authors: Department of Neurology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, USA; Department of Neurology, Veterans Administration Greater Los Angeles Healthcare System, USA. dnaylor@ucla.edu
authors: David E
authors: DE
authors: Naylor
authors: Hantao
authors: H
authors: Liu
authors: Jerome
authors: J
authors: Niquet
authors: Claude G
authors: CG
authors: Wasterlain
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018408:Patch-Clamp Techniques; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid