Spermine potentiation of recombinant N-methyl-D-aspartate receptors is affected by subunit composition

Ling Zhang, Xin Zheng, Marie Christine Paupard, Alice P. Wang, Linda Santchi, Linda K. Friedman, R. Suzanne Zukin, Michael V. L. Bennett

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

The present study shows that both the NR1 and NR2 subunits critically affect spermine potentiation of heteromeric recombinant N-methyl-D-aspartate receptors. NR1011, the most prominent NR1 splice variant in rat forebrain, and NR1100, prominent in midbrain, were expressed in Xenopus oocytes singly and in combination with NR2A, NR2B, and NR2C subunits. As for NR1011 homomers, NR1011/NR2B receptors exhibited spermine potentiation by two mechanisms: by increasing glycine affinity and by increasing current through receptors with bound N-methyl-D-aspartate and glycine. NR1011/NR2A receptors exhibited only the increase in glycine affinity, and NR1011/NR2C receptors exhibited neither. As for NR1100 homomers, NR1100/NR2B and NR1100/NR2A receptors exhibited spermine potentiation only by increasing the glycine affinity. Spermine produced no potentiation of NR1100/NR2C receptors. Thus, the NR2B subunit 'permits' both forms of spermine potentiation, the NR2A subunit permits spermine potentiation only by increasing the glycine affinity, and the NR2C subunit permits neither form of potentiation. Spermine actions on NR1/NR2 showed little voltage dependence. These observations are of interest because the NR1 and NR2 subunits are differentially distributed and developmentally regulated. At early postnatal ages, NR2B subunit mRNA was more highly expressed than NR2A and NR2C mRNAs in hippocampus, neocortex, and caudate-putamen. These findings account for many of the observed differences among neurons in polyamine actions and suggest that these actions will vary in a cell-specific and age-related manner.

Original languageEnglish (US)
Pages (from-to)10883-10887
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number23
DOIs
StatePublished - Nov 8 1994

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Spermine
N-Methyl-D-Aspartate Receptors
Glycine
Licensure
Sarcosine
Messenger RNA
Putamen
Neocortex
Polyamines
N-Methylaspartate
Prosencephalon
Mesencephalon
Xenopus
Oocytes
Hippocampus
Neurons

Keywords

  • excitatory amino acid receptors
  • glutamate receptors
  • polyamines
  • recombinant receptors
  • Xenopus oocyte expression system

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Spermine potentiation of recombinant N-methyl-D-aspartate receptors is affected by subunit composition. / Zhang, Ling; Zheng, Xin; Paupard, Marie Christine; Wang, Alice P.; Santchi, Linda; Friedman, Linda K.; Zukin, R. Suzanne; Bennett, Michael V. L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 23, 08.11.1994, p. 10883-10887.

Research output: Contribution to journalArticle

Zhang, Ling ; Zheng, Xin ; Paupard, Marie Christine ; Wang, Alice P. ; Santchi, Linda ; Friedman, Linda K. ; Zukin, R. Suzanne ; Bennett, Michael V. L. / Spermine potentiation of recombinant N-methyl-D-aspartate receptors is affected by subunit composition. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 23. pp. 10883-10887.
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abstract = "The present study shows that both the NR1 and NR2 subunits critically affect spermine potentiation of heteromeric recombinant N-methyl-D-aspartate receptors. NR1011, the most prominent NR1 splice variant in rat forebrain, and NR1100, prominent in midbrain, were expressed in Xenopus oocytes singly and in combination with NR2A, NR2B, and NR2C subunits. As for NR1011 homomers, NR1011/NR2B receptors exhibited spermine potentiation by two mechanisms: by increasing glycine affinity and by increasing current through receptors with bound N-methyl-D-aspartate and glycine. NR1011/NR2A receptors exhibited only the increase in glycine affinity, and NR1011/NR2C receptors exhibited neither. As for NR1100 homomers, NR1100/NR2B and NR1100/NR2A receptors exhibited spermine potentiation only by increasing the glycine affinity. Spermine produced no potentiation of NR1100/NR2C receptors. Thus, the NR2B subunit 'permits' both forms of spermine potentiation, the NR2A subunit permits spermine potentiation only by increasing the glycine affinity, and the NR2C subunit permits neither form of potentiation. Spermine actions on NR1/NR2 showed little voltage dependence. These observations are of interest because the NR1 and NR2 subunits are differentially distributed and developmentally regulated. At early postnatal ages, NR2B subunit mRNA was more highly expressed than NR2A and NR2C mRNAs in hippocampus, neocortex, and caudate-putamen. These findings account for many of the observed differences among neurons in polyamine actions and suggest that these actions will vary in a cell-specific and age-related manner.",
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AU - Zhang, Ling

AU - Zheng, Xin

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AU - Wang, Alice P.

AU - Santchi, Linda

AU - Friedman, Linda K.

AU - Zukin, R. Suzanne

AU - Bennett, Michael V. L.

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AB - The present study shows that both the NR1 and NR2 subunits critically affect spermine potentiation of heteromeric recombinant N-methyl-D-aspartate receptors. NR1011, the most prominent NR1 splice variant in rat forebrain, and NR1100, prominent in midbrain, were expressed in Xenopus oocytes singly and in combination with NR2A, NR2B, and NR2C subunits. As for NR1011 homomers, NR1011/NR2B receptors exhibited spermine potentiation by two mechanisms: by increasing glycine affinity and by increasing current through receptors with bound N-methyl-D-aspartate and glycine. NR1011/NR2A receptors exhibited only the increase in glycine affinity, and NR1011/NR2C receptors exhibited neither. As for NR1100 homomers, NR1100/NR2B and NR1100/NR2A receptors exhibited spermine potentiation only by increasing the glycine affinity. Spermine produced no potentiation of NR1100/NR2C receptors. Thus, the NR2B subunit 'permits' both forms of spermine potentiation, the NR2A subunit permits spermine potentiation only by increasing the glycine affinity, and the NR2C subunit permits neither form of potentiation. Spermine actions on NR1/NR2 showed little voltage dependence. These observations are of interest because the NR1 and NR2 subunits are differentially distributed and developmentally regulated. At early postnatal ages, NR2B subunit mRNA was more highly expressed than NR2A and NR2C mRNAs in hippocampus, neocortex, and caudate-putamen. These findings account for many of the observed differences among neurons in polyamine actions and suggest that these actions will vary in a cell-specific and age-related manner.

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KW - recombinant receptors

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