Skip to main content

Electrophysiologic Characteristics of Heteromeric Recombinant NMDA Receptors

Comparison with Native Receptors

  • Chapter
The Ionotropic Glutamate Receptors

Part of the book series: The Receptors ((REC))

  • 139 Accesses

Abstract

The N-methyl-D-aspartate (NMDA) receptor-channel complex is activated by the major excitatory neurotransmitter occurring in central synapses, glutamate. This ligand-gated ion channel displays several unique biophysical and ionic properties originally described in native systems. Particularly noteworthy of these properties are a high permeability to Ca++, a voltage-dependent block by Mg++, slow channel kinetics, and various single-channel conductance states. With the discovery and expression of NR1 and NR2 sub-unit gene products, there has been extensive analysis of these properties in NMDA channels expressed in both Xenopus oocytes and mammalian expression systems. The purpose of this chapter, therefore, is to compare the available data describing channel behavior in native systems with that obtained from expressed receptors. This chapter is divided along the primary aspects of NMDA channel properties: single channel behavior, ionic (Ca++ and Mg++) characteristics and related results of mutational studies in recombinant receptors, and finally, macroscopic kinetic properties.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ascher, P. and Nowak, L. (1988) The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J. Physiol. 399, 247–266.

    PubMed  CAS  Google Scholar 

  • Béhé, P., Stern, P., Wyllie, D. J. A., Nassar, M., Schoepfer, R., and Colquhoun, D. (1995) Determination of NMDA NR1 subunit copy number in recombinant NMDA receptors. Proc. R. Soc. Lond. B 262, 205–213.

    Article  Google Scholar 

  • Burnashev, N., Schoepfer, R., Monyer, H., Ruppersberg, J. P., Günther, W., Seeburg, P. H., and Sakmann, B. (1992) Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor. Science 257, 1415–1419.

    Article  PubMed  CAS  Google Scholar 

  • Burnashev, N., Zhou, Z., Neher, E., and Sakmann, B. (1995) Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes. J. Physiol. 485.2, 403–418.

    Google Scholar 

  • Carmignoto, G. and Vicini, S. (1992) Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science 258, 1007–1011.

    Article  PubMed  CAS  Google Scholar 

  • Chazot, P. L., Coleman, S. K., Cik, M., and Stephenson, F. A. (1994) Molecular characterization of N-methyl-D-aspartate receptors expressed in mammalian cells yields evidence for the coexistence of three subunit types within a discrete receptor molecule. J. Biol. Chem. 269, 24,403–24,409.

    Google Scholar 

  • Cull-Candy, S. G. and Usowicz, M. M. (1987) Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature 325, 525–528.

    Article  PubMed  CAS  Google Scholar 

  • Farrant, M., Feldmeyer, D., Takahashi, T., and Cull-Candy, S. G. (1994) NMDA-receptor channel diversity in the developing cerebellum. Nature 368, 335–339.

    Article  PubMed  CAS  Google Scholar 

  • Gibb, A. J. and Colquhuon, D. (1991) Glutamate activation of a single NMDA receptor-channels produces a cluster of channel openings. Proc. R. Soc. Lond. B 243, 39–45.

    Article  CAS  Google Scholar 

  • Gibb, A.J. and Colquhuon, D. (1992) Activation of NMDA receptors by L-glutamate in cells dissociated from adult rat hippocampus. J. Physiol. 456, 143–179.

    PubMed  CAS  Google Scholar 

  • Hestrin, S. (1992) Developmental regulation of NMDA-receptor-mediated synaptic currents at a central synapse. Nature 357, 686–689.

    Article  PubMed  CAS  Google Scholar 

  • Howe, J.R., Cull-Candy, S.G., and Colquhoun, D. (1991) Currents through single glutamate receptor channels in outside-out patches from rat cerebellar granule cells. J. Physiol. 432, 143–202.

    PubMed  CAS  Google Scholar 

  • Ishii, T., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., Akazawa, C., Shigemoto, R., Mizuno, N., Masu, M., and Nakanishi, S. (1993) Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. J. Biol. Chem. 4, 2836–3843.

    Google Scholar 

  • Johnson, J. W. and Ascher, P. (1987) Glycine potentiates the NMDA response in cultured mouse brain neurones. Nature 325, 529–531.

    Article  PubMed  CAS  Google Scholar 

  • Kato, N. and Yoshimura, H. (1993) Reduced Mg++ block of N-methyl-D-aspartate receptor mediated synaptic potentials in developing visual cortex. Proc. Natl. Acad. Sci. USA 90, 7114–7118.

    Article  PubMed  CAS  Google Scholar 

  • Kutsuwada, T., Kashiwabuchi, N., Mori, H., Sakimura, K., Kushiya, E., Araki, K., Meguro, H., Masaki, H., Kumanishi, T., Arakawa, M., and Mishina, M. (1992) Molecular diversity of the NMDA receptor channel. Nature 358, 36–41.

    Article  PubMed  CAS  Google Scholar 

  • Lester, R. A. J., Clements, J. D., Westbrook, G. L., and Jahr, C. E. (1990) Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents. Nature 346, 565–567.

    Article  PubMed  CAS  Google Scholar 

  • MacDermott, A. B., Mayer, M. L., Westbrook, G. L., Smith, S. J., and Barker, J. L. (1986) NMDA-receptor activation increases cytoplasmic calcium concentrations in cultures spinal cord neurones. Nature 321, 519–522.

    Article  PubMed  CAS  Google Scholar 

  • Momiyama, A., Feldmeyer, D., and Cull-Candy, S. G. (1996) Identification of a low-conductance NMDA-channel with reduced sensitivity to Mg++ in rat central neurones. J. Physiol., in press.

    Google Scholar 

  • Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B., and Seeburg, P. H. (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529–540.

    Article  PubMed  CAS  Google Scholar 

  • Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B., and Seeburg, P. H. (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256, 1217–1221.

    Article  PubMed  CAS  Google Scholar 

  • Mori, H., Masaki, H., Yamakura, T., and Mishina, M. (1992) Identification by mutagenesis of a Mg2+-block site of the NMDA receptor channel. Nature 358, 673–675.

    Article  PubMed  CAS  Google Scholar 

  • Morrisett, R. A., Mott, D. D., Lewis, D. V., Wilson. W. A., and Swartzwelder, H. S. (1990) Reduced sensitivity of the N-methyl-D-aspartate component of synaptic transmission to magnesium in hippocampal slices from immature rats. Dev. Brain Res. 56, 257–262.

    Article  CAS  Google Scholar 

  • Sommer, B., Kohler, M., Sprengel, R., and Seeburg, P. H. (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67, 11–19.

    Article  PubMed  CAS  Google Scholar 

  • Stern, P., Béhé, P., Schoepfer, R., and Colquhoun, D. (1992) Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proc. R. Soc. Lond. B 250, 271–277.

    Article  CAS  Google Scholar 

  • Stern, P., Cik, M., Colquhoun, D., and Stephenson, F. A. (1994) Single-channel properties of cloned NMDA receptors in a human cell line: comparison with results from Xenopus oocytes. J. Physiol. 476.3, 391–397.

    Google Scholar 

  • Watanbe, M., Inoue, Y., Sakimura, K., and Mishina, M. (1992) Developmental changes in distribution of NMDA receptor channel subunit mRNAs. Neuroreport 3, 1138–1140.

    Article  Google Scholar 

  • Wyllie, D. J. A., Behe, P., Nassar, M., Schoepfer, R., and Colquhoun, D. (1996) Single-channel currents from recombinant NMDA NR1a/NR2D receptors expressed in Xenopus oocytes. Proc. R. Soc. Lond. B 263, 1079–1086.

    Article  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Humana Press Inc.

About this chapter

Cite this chapter

Morrisett, R. (1997). Electrophysiologic Characteristics of Heteromeric Recombinant NMDA Receptors. In: Monaghan, D.T., Wenthold, R.J. (eds) The Ionotropic Glutamate Receptors. The Receptors. Humana Press. https://doi.org/10.1007/978-1-4612-3962-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-3962-8_12

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-8442-0

  • Online ISBN: 978-1-4612-3962-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics