Abstract |
The subunit composition of glutamate receptors affects their functional properties, and could contribute to abnormal electrophysiology in pediatric cortical dysplasia (CD). We examined electrophysiological responses and subunit assembly of N-methyl-D-aspartate ( NMDA) receptors in acutely dissociated normal-appearing pyramidal and cytomegalic neurons from CD tissue and normal-appearing pyramidal neurons from non-CD tissue. In most cytomegalic and approximately 30% of normal-appearing pyramidal neurons from CD tissue, NMDA currents showed decreased Mg(2+) sensitivity compared with neurons from non-CD tissue. Ifenprodil had less effect in CD compared with non-CD neurons, indicating a functional loss of NR2B subunits. NMDA-evoked current density was decreased in cytomegalic compared with normal-appearing neurons. Single-cell reverse transcriptase polymerase chain reaction showed that all non-CD neurons expressed NR2B subunit mRNA. By comparison, 22% of pyramidal neurons in CD tissue lacked NR2B mRNA. Immunofluorescence showed a decrease in NR2B subunit expression in cytomegalic neurons and a subset of normal-appearing pyramidal neurons from CD tissue. Taken together, these results demonstrate the presence of NMDA receptors with altered subunit composition and Mg(2+) sensitivity that could contribute to functional abnormalities in CD.
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Authors | Véronique M André, Jorge Flores-Hernández, Carlos Cepeda, Amaal J Starling, Snow Nguyen, Mary Kay Lobo, Harry V Vinters, Michael S Levine, Gary W Mathern |
Journal | Cerebral cortex (New York, N.Y. : 1991)
(Cereb Cortex)
Vol. 14
Issue 6
Pg. 634-46
(Jun 2004)
ISSN: 1047-3211 [Print] United States |
PMID | 15054078
(Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Piperidines
- Receptors, N-Methyl-D-Aspartate
- N-Methylaspartate
- Magnesium
- ifenprodil
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Topics |
- Adolescent
- Cells, Cultured
- Cerebral Cortex
(abnormalities, drug effects, physiopathology)
- Child
- Child, Preschool
- Epilepsy
(pathology, physiopathology)
- Humans
- Infant
- Magnesium
(pharmacology)
- Membrane Potentials
(drug effects)
- N-Methylaspartate
(pharmacology)
- Piperidines
(pharmacology)
- Pyramidal Cells
(drug effects, metabolism, physiopathology)
- Receptors, N-Methyl-D-Aspartate
(chemistry, drug effects, metabolism)
- Reference Values
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