Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Jun 1;485(Pt 2):373–381. doi: 10.1113/jphysiol.1995.sp020736

Calcium entry through a subpopulation of AMPA receptors desensitized neighbouring NMDA receptors in rat dorsal horn neurons.

A Kyrozis 1, P A Goldstein 1, M J Heath 1, A B MacDermott 1
PMCID: PMC1157999  PMID: 7545229

Abstract

1. A Ca(2+)-dependent interaction between non-NMDA and NMDA receptors was studied in embryonic rat dorsal horn neurons grown in tissue culture using perforated-patch recording. Specifically, non-NMDA receptors were found to induce reversible inhibition of NMDA receptors in a manner dependent on the presence of extracellular Ca2+. 2. Non-NMDA receptor-induced inhibition of NMDA receptors was mediated by the elevation of intracellular Ca2+ concentration produced by Ca2+ entry through a subpopulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) non-NMDA receptors. Furthermore, Ca2+ entry through the AMPA channels alone is sufficient for desensitization of NMDA channels to occur. 3. Imaging of neuritic sites of Ca2+ revealed that Ca(2+)-permeable AMPA channels are often co-localized with NMDA channels on dorsal horn neurons, indicating that the Ca(2+)-mediated interaction between receptors may occur within small dendritic domains. 4. The ability of Ca(2+)-permeable AMPA channels to inhibit adjacent NMDA channels may contribute to the postsynaptic integration of excitatory input.

Full text

PDF
373

Images in this article

Selected References

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

  1. Arancio O., MacDermott A. B. Differential distribution of excitatory amino acid receptors on embryonic rat spinal cord neurons in culture. J Neurophysiol. 1991 Apr;65(4):899–913. doi: 10.1152/jn.1991.65.4.899. [DOI] [PubMed] [Google Scholar]
  2. Arancio O., Yoshimura M., Murase K., MacDermott A. B. The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats. Neuroscience. 1993 Jan;52(1):159–167. doi: 10.1016/0306-4522(93)90190-q. [DOI] [PubMed] [Google Scholar]
  3. Artola A., Singer W. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends Neurosci. 1993 Nov;16(11):480–487. doi: 10.1016/0166-2236(93)90081-v. [DOI] [PubMed] [Google Scholar]
  4. Burnashev N., Monyer H., Seeburg P. H., Sakmann B. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron. 1992 Jan;8(1):189–198. doi: 10.1016/0896-6273(92)90120-3. [DOI] [PubMed] [Google Scholar]
  5. Chen L., Huang L. Y. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature. 1992 Apr 9;356(6369):521–523. doi: 10.1038/356521a0. [DOI] [PubMed] [Google Scholar]
  6. Furuyama T., Kiyama H., Sato K., Park H. T., Maeno H., Takagi H., Tohyama M. Region-specific expression of subunits of ionotropic glutamate receptors (AMPA-type, KA-type and NMDA receptors) in the rat spinal cord with special reference to nociception. Brain Res Mol Brain Res. 1993 Apr;18(1-2):141–151. doi: 10.1016/0169-328x(93)90183-p. [DOI] [PubMed] [Google Scholar]
  7. Herb A., Burnashev N., Werner P., Sakmann B., Wisden W., Seeburg P. H. The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron. 1992 Apr;8(4):775–785. doi: 10.1016/0896-6273(92)90098-x. [DOI] [PubMed] [Google Scholar]
  8. Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kutsuwada T., Kashiwabuchi N., Mori H., Sakimura K., Kushiya E., Araki K., Meguro H., Masaki H., Kumanishi T., Arakawa M. Molecular diversity of the NMDA receptor channel. Nature. 1992 Jul 2;358(6381):36–41. doi: 10.1038/358036a0. [DOI] [PubMed] [Google Scholar]
  10. Köhler M., Burnashev N., Sakmann B., Seeburg P. H. Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron. 1993 Mar;10(3):491–500. doi: 10.1016/0896-6273(93)90336-p. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Mayer M. L., MacDermott A. B., Westbrook G. L., Smith S. J., Barker J. L. Agonist- and voltage-gated calcium entry in cultured mouse spinal cord neurons under voltage clamp measured using arsenazo III. J Neurosci. 1987 Oct;7(10):3230–3244. doi: 10.1523/JNEUROSCI.07-10-03230.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. McMahon S. B., Lewin G. R., Wall P. D. Central hyperexcitability triggered by noxious inputs. Curr Opin Neurobiol. 1993 Aug;3(4):602–610. doi: 10.1016/0959-4388(93)90062-4. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. Müller T., Möller T., Berger T., Schnitzer J., Kettenmann H. Calcium entry through kainate receptors and resulting potassium-channel blockade in Bergmann glial cells. Science. 1992 Jun 12;256(5063):1563–1566. doi: 10.1126/science.1317969. [DOI] [PubMed] [Google Scholar]
  19. Reichling D. B., MacDermott A. B. Brief calcium transients evoked by glutamate receptor agonists in rat dorsal horn neurons: fast kinetics and mechanisms. J Physiol. 1993 Sep;469:67–88. doi: 10.1113/jphysiol.1993.sp019805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reichling D. B., MacDermott A. B. Lanthanum actions on excitatory amino acid-gated currents and voltage-gated calcium currents in rat dorsal horn neurons. J Physiol. 1991 Sep;441:199–218. doi: 10.1113/jphysiol.1991.sp018746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rusin K. I., Ryu P. D., Randic M. Modulation of excitatory amino acid responses in rat dorsal horn neurons by tachykinins. J Neurophysiol. 1992 Jul;68(1):265–286. doi: 10.1152/jn.1992.68.1.265. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Segal M. M., Furshpan E. J. Epileptiform activity in microcultures containing small numbers of hippocampal neurons. J Neurophysiol. 1990 Nov;64(5):1390–1399. doi: 10.1152/jn.1990.64.5.1390. [DOI] [PubMed] [Google Scholar]
  24. Sommer B., Seeburg P. H. Glutamate receptor channels: novel properties and new clones. Trends Pharmacol Sci. 1992 Jul;13(7):291–296. doi: 10.1016/0165-6147(92)90088-n. [DOI] [PubMed] [Google Scholar]
  25. Tölle T. R., Berthele A., Zieglgänsberger W., Seeburg P. H., Wisden W. The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat spinal cord and in periaqueductal gray. J Neurosci. 1993 Dec;13(12):5009–5028. doi: 10.1523/JNEUROSCI.13-12-05009.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Yoshimura M., Jessell T. Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa neurones in the rat spinal cord. J Physiol. 1990 Nov;430:315–335. doi: 10.1113/jphysiol.1990.sp018293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zeilhofer H. U., Müller T. H., Swandulla D. Inhibition of high voltage-activated calcium currents by L-glutamate receptor-mediated calcium influx. Neuron. 1993 May;10(5):879–887. doi: 10.1016/0896-6273(93)90203-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES