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 ∼30% of normal-appearing pyramidal neurons from CD tissue, NMDA currents showed decreased Mg2+ 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 Mg2+ sensitivity that could contribute to functional abnormalities in CD.
Original language | English (US) |
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Pages (from-to) | 634-646 |
Number of pages | 13 |
Journal | Cerebral Cortex |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2004 |
Keywords
- Cerebral cortex
- Electrophysiology
- Epilepsy
- Immunohistochemistry
- RT-PCR
- Receptor subunits
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience