N-Methyl-D-aspartate receptor plasticity in kindling: Quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex

G. C. Yeh, D. W. Bonhaus, J. V. Nadler, J. O. McNamara

研究成果: 雜誌貢獻文章同行評審

127 引文 斯高帕斯(Scopus)

摘要

Kindling is an animal model of epilepsy and neuronal plasticity produced by periodic electrical stimulation of the brain. Electrophysiologic studies indicate that this phenomenon is associated with increased participation of N-methyl-D-aspartate (NMDA) receptors in excitatory synaptic transmission. Biochemical studies suggest that a change intrinsic to the NMDA receptor-channel complex may contribute to the increase in NMDA receptor mediated synaptic transmission. We tested this idea by measuring the binding of 3-[(+)-2-(carboxypiperazin-4-yl)][1,2-3H]propyl-1-phosphonic acid ([3H]CPP), [3H]glycine, and tritiated N-[(1-thienyl)cyclohexyl]piperidine ([3H]TCP) to rat hippocampal membranes. In this preparation these ligands are selective for the NMDA receptor, the strychnine-insensitive glycine receptor, and the NMDA receptor-gated ion channel, respectively. Kindling increased the density of CPP, glycine, and TCP binding sites in hippocampal membranes by 47%, 42%, and 25%, respectively. No significant changes were detected in the affinity of these binding sites. Surprisingly, alterations in the glycine binding site were detected in animals sacrificed 1 month but not 1 day after the final kindling stimulation. Thus, delayed upregulation of the NMDA receptor-channel complex may be one molecular mechanism that maintains the long-lasting hyperexcitability of hippocampal neurons in kindled animals.

原文英語
頁(從 - 到)8157-8160
頁數4
期刊Proceedings of the National Academy of Sciences of the United States of America
86
發行號20
出版狀態已發佈 - 1989
對外發佈Yes

ASJC Scopus subject areas

  • General
  • Genetics

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