Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Feb 1;482(Pt 3):567–573. doi: 10.1113/jphysiol.1995.sp020540

Calcium-dependent inactivation of heteromeric NMDA receptor-channels expressed in human embryonic kidney cells.

I Medina 1, N Filippova 1, G Charton 1, S Rougeole 1, Y Ben-Ari 1, M Khrestchatisky 1, P Bregestovski 1
PMCID: PMC1157782  PMID: 7537819

Abstract

1. Whole-cell current through heteromeric NR1-NR2A and NR1-NR2B subunit combinations of NMDA channels transiently expressed in human embryonic kidney cells (HEK 293) were studied using the patch-clamp technique. 2. With 4 mM Mg-ATP in the internal pipette solution, the responses of cells expressing NR1-NR2A channels to glutamate application gradually decreased, reaching 50% of control during the first 20 min of recording. This process was accompanied by acceleration of desensitization. 3. Conditioning (5-15 s) applications of glutamate (100 microM) induced a transient inactivation of NR1-NR2A and NR1-NR2B channels (20-40%) with a slow time course of recovery (tau r = 10-60 s). Both the degree of inactivation and the time constant of recovery increased with the duration of conditioning applications of glutamate, and with an elevation of Ca2+ in the external solution. 4. These results show that both NR1-NR2A and NR1-NR2B recombinant NMDA receptor-channels expressed in HEK 293 cells can be transiently inhibited by Ca2+ ions in a similar way to that described for hippocampal neurones.

Full text

PDF
567

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett V., Gilligan D. M. The spectrin-based membrane skeleton and micron-scale organization of the plasma membrane. Annu Rev Cell Biol. 1993;9:27–66. doi: 10.1146/annurev.cb.09.110193.000331. [DOI] [PubMed] [Google Scholar]
  2. Chizhmakov I. V., Kiskin N. I., Krishtal O. A. Two types of steady-state desensitization of N-methyl-D-aspartate receptor in isolated hippocampal neurones of rat. J Physiol. 1992 Mar;448:453–472. doi: 10.1113/jphysiol.1992.sp019051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Legendre P., Rosenmund C., Westbrook G. L. Inactivation of NMDA channels in cultured hippocampal neurons by intracellular calcium. J Neurosci. 1993 Feb;13(2):674–684. doi: 10.1523/JNEUROSCI.13-02-00674.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lieberman D. N., Mody I. Regulation of NMDA channel function by endogenous Ca(2+)-dependent phosphatase. Nature. 1994 May 19;369(6477):235–239. doi: 10.1038/369235a0. [DOI] [PubMed] [Google Scholar]
  5. MacDonald J. F., Mody I., Salter M. W. Regulation of N-methyl-D-aspartate receptors revealed by intracellular dialysis of murine neurones in culture. J Physiol. 1989 Jul;414:17–34. doi: 10.1113/jphysiol.1989.sp017674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mayer M. L., Westbrook G. L. The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture. J Physiol. 1985 Apr;361:65–90. doi: 10.1113/jphysiol.1985.sp015633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mayer M. L., Westbrook G. L. The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol. 1987;28(3):197–276. doi: 10.1016/0301-0082(87)90011-6. [DOI] [PubMed] [Google Scholar]
  8. Medina I., Filippova N., Barbin G., Ben-Ari Y., Bregestovski P. Kainate-induced inactivation of NMDA currents via an elevation of intracellular Ca2+ in hippocampal neurons. J Neurophysiol. 1994 Jul;72(1):456–465. doi: 10.1152/jn.1994.72.1.456. [DOI] [PubMed] [Google Scholar]
  9. Monyer H., Burnashev N., Laurie D. J., Sakmann B., Seeburg P. H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994 Mar;12(3):529–540. doi: 10.1016/0896-6273(94)90210-0. [DOI] [PubMed] [Google Scholar]
  10. Monyer H., Sprengel R., Schoepfer R., Herb A., Higuchi M., Lomeli H., Burnashev N., Sakmann B., Seeburg P. H. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science. 1992 May 22;256(5060):1217–1221. doi: 10.1126/science.256.5060.1217. [DOI] [PubMed] [Google Scholar]
  11. Rosenmund C., Westbrook G. L. Calcium-induced actin depolymerization reduces NMDA channel activity. Neuron. 1993 May;10(5):805–814. doi: 10.1016/0896-6273(93)90197-y. [DOI] [PubMed] [Google Scholar]
  12. Rosenmund C., Westbrook G. L. Rundown of N-methyl-D-aspartate channels during whole-cell recording in rat hippocampal neurons: role of Ca2+ and ATP. J Physiol. 1993 Oct;470:705–729. doi: 10.1113/jphysiol.1993.sp019884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sather W., Dieudonné S., MacDonald J. F., Ascher P. Activation and desensitization of N-methyl-D-aspartate receptors in nucleated outside-out patches from mouse neurones. J Physiol. 1992 May;450:643–672. doi: 10.1113/jphysiol.1992.sp019148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schneggenburger R., Zhou Z., Konnerth A., Neher E. Fractional contribution of calcium to the cation current through glutamate receptor channels. Neuron. 1993 Jul;11(1):133–143. doi: 10.1016/0896-6273(93)90277-x. [DOI] [PubMed] [Google Scholar]
  15. Stern P., Cik M., Colquhoun D., Stephenson F. A. Single channel properties of cloned NMDA receptors in a human cell line: comparison with results from Xenopus oocytes. J Physiol. 1994 May 1;476(3):391–397. doi: 10.1113/jphysiol.1994.sp020140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tong G., Jahr C. E. Regulation of glycine-insensitive desensitization of the NMDA receptor in outside-out patches. J Neurophysiol. 1994 Aug;72(2):754–761. doi: 10.1152/jn.1994.72.2.754. [DOI] [PubMed] [Google Scholar]
  17. Vyklický L., Jr Calcium-mediated modulation of N-methyl-D-aspartate (NMDA) responses in cultured rat hippocampal neurones. J Physiol. 1993 Oct;470:575–600. doi: 10.1113/jphysiol.1993.sp019876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zorumski C. F., Yang J., Fischbach G. D. Calcium-dependent, slow desensitization distinguishes different types of glutamate receptors. Cell Mol Neurobiol. 1989 Mar;9(1):95–104. doi: 10.1007/BF00711446. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES