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

Publication ,  Journal Article
Yeh, GC; Bonhaus, DW; Nadler, JV; McNamara, JO
Published in: Proc Natl Acad Sci U S A
October 1989

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 1989

Volume

86

Issue

20

Start / End Page

8157 / 8160

Location

United States

Related Subject Headings

  • Seizures
  • Receptors, Neurotransmitter
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Glycine
  • Rats, Inbred Strains
  • Rats
  • Piperazines
  • Phencyclidine
  • Neuronal Plasticity
  • Male
 

Citation

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Yeh, G. C., Bonhaus, D. W., Nadler, J. V., & McNamara, J. O. (1989). N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex. Proc Natl Acad Sci U S A, 86(20), 8157–8160. https://doi.org/10.1073/pnas.86.20.8157
Yeh, G. C., D. W. Bonhaus, J. V. Nadler, and J. O. McNamara. “N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.Proc Natl Acad Sci U S A 86, no. 20 (October 1989): 8157–60. https://doi.org/10.1073/pnas.86.20.8157.
Yeh, G. C., et al. “N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.Proc Natl Acad Sci U S A, vol. 86, no. 20, Oct. 1989, pp. 8157–60. Pubmed, doi:10.1073/pnas.86.20.8157.
Yeh GC, Bonhaus DW, Nadler JV, McNamara JO. N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8157–8160.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 1989

Volume

86

Issue

20

Start / End Page

8157 / 8160

Location

United States

Related Subject Headings

  • Seizures
  • Receptors, Neurotransmitter
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Glycine
  • Rats, Inbred Strains
  • Rats
  • Piperazines
  • Phencyclidine
  • Neuronal Plasticity
  • Male