Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 May;115(2):295–301. doi: 10.1111/j.1476-5381.1995.tb15876.x

Subcellular localization and molecular pharmacology of distinct populations of [3H]-AMPA binding sites in rat hippocampus.

J M Henley 1
PMCID: PMC1908311  PMID: 7545519

Abstract

1. The subcellular distributions of [3H]-alpha-amino-3-hydroxy-5- methylisoxazolepropionate ([3H]-AMPA) and [3H]-kainate binding sites in rat hippocampus were investigated by cell fractionation techniques. 2. Two major populations of [3H]-AMPA sites were detected with the majority of binding located intracellularly in the microsomal (P3) fraction. Most of the remaining sites were in the synaptosomal membrane fraction but some were also present in the nuclear fraction. In contrast, essentially all of the [3H]-kainate binding sites were in the synaptosomal membrane fraction. 3. Saturation binding analysis yielded KD and Bmax values for [3H]-AMPA of 147 nM and 2.6 pmol mg-1 protein respectively for the synaptosomal membrane-associated sites and 129 nM and 5.3 pmol mg-1 protein respectively for the microsomal sites. 4. Both main populations of [3H]-AMPA sites displayed the same rank order of inhibition by competitive ligands, the apparent Mr values of GluR1 subunits were equivalent, suggesting the same degree of post-translational modification and the hydrodynamic properties of the receptor complexes were identical. 5. These data are consistent with the hypothesis that the movement of AMPA receptors between cellular compartments in the postsynaptic neurone could constitute one mechanism underlying long-term potentiation in the hippocampus.

Full text

PDF
295

Images in this article

298Figure 3
on p.298
300Figure 7
on p.300

Selected References

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

  1. Barnes J. M., Henley J. M. Autoradiographic distribution of glutamatergic ligand binding sites in Xenopus brain: evidence for intracellular [3H]AMPA binding sites. Brain Res. 1993 Oct 29;626(1-2):259–264. doi: 10.1016/0006-8993(93)90585-b. [DOI] [PubMed] [Google Scholar]
  2. Barnes J. M., Henley J. M. Molecular characteristics of excitatory amino acid receptors. Prog Neurobiol. 1992 Aug;39(2):113–133. doi: 10.1016/0301-0082(92)90007-2. [DOI] [PubMed] [Google Scholar]
  3. Baude A., Molnár E., Latawiec D., McIlhinney R. A., Somogyi P. Synaptic and nonsynaptic localization of the GluR1 subunit of the AMPA-type excitatory amino acid receptor in the rat cerebellum. J Neurosci. 1994 May;14(5 Pt 1):2830–2843. doi: 10.1523/JNEUROSCI.14-05-02830.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  5. Choi D. W. Excitotoxic cell death. J Neurobiol. 1992 Nov;23(9):1261–1276. doi: 10.1002/neu.480230915. [DOI] [PubMed] [Google Scholar]
  6. Craig A. M., Blackstone C. D., Huganir R. L., Banker G. The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits. Neuron. 1993 Jun;10(6):1055–1068. doi: 10.1016/0896-6273(93)90054-u. [DOI] [PubMed] [Google Scholar]
  7. Eshhar N., Petralia R. S., Winters C. A., Niedzielski A. S., Wenthold R. J. The segregation and expression of glutamate receptor subunits in cultured hippocampal neurons. Neuroscience. 1993 Dec;57(4):943–964. doi: 10.1016/0306-4522(93)90040-m. [DOI] [PubMed] [Google Scholar]
  8. Good P. F., Huntley G. W., Rogers S. W., Heinemann S. F., Morrison J. H. Organization and quantitative analysis of kainate receptor subunit GluR5-7 immunoreactivity in monkey hippocampus. Brain Res. 1993 Oct 8;624(1-2):347–353. doi: 10.1016/0006-8993(93)90102-s. [DOI] [PubMed] [Google Scholar]
  9. Henley J. M., Ambrosini A., Rodriguez-Ithurralde D., Sudan H., Brackley P., Kerry C., Mellor I., Abutidze K., Usherwood P. N., Barnard E. A. Purified unitary kainate/alpha-amino-3-hydroxy-5-methylisooxazole-propionate (AMPA) and kainate/AMPA/N-methyl-D-aspartate receptors with interchangeable subunits. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4806–4810. doi: 10.1073/pnas.89.11.4806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Henley J. M., Barnard E. A. Kainate receptors in Xenopus central nervous system: solubilisation with n-octyl-beta-D-glucopyranoside. J Neurochem. 1989 Jan;52(1):31–37. doi: 10.1111/j.1471-4159.1989.tb10894.x. [DOI] [PubMed] [Google Scholar]
  11. Hollmann M., Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci. 1994;17:31–108. doi: 10.1146/annurev.ne.17.030194.000335. [DOI] [PubMed] [Google Scholar]
  12. Honoré T., Drejer J. Chaotropic ions affect the conformation of quisqualate receptors in rat cortical membranes. J Neurochem. 1988 Aug;51(2):457–461. doi: 10.1111/j.1471-4159.1988.tb01060.x. [DOI] [PubMed] [Google Scholar]
  13. Honoré T., Nielsen M. Complex structure of quisqualate-sensitive glutamate receptors in rat cortex. Neurosci Lett. 1985 Feb 28;54(1):27–32. doi: 10.1016/s0304-3940(85)80113-0. [DOI] [PubMed] [Google Scholar]
  14. Maeno H., Johnson E. M., Greengard P. Subcellular distribution of adenosine 3',5'-monophosphate-dependent protein kinase in rat brain. J Biol Chem. 1971 Jan 10;246(1):134–142. [PubMed] [Google Scholar]
  15. Martin L. J., Blackstone C. D., Levey A. I., Huganir R. L., Price D. L. AMPA glutamate receptor subunits are differentially distributed in rat brain. Neuroscience. 1993 Mar;53(2):327–358. doi: 10.1016/0306-4522(93)90199-p. [DOI] [PubMed] [Google Scholar]
  16. Miller L. P., Johnson A. E., Gelhard R. E., Insel T. R. The ontogeny of excitatory amino acid receptors in the rat forebrain--II. Kainic acid receptors. Neuroscience. 1990;35(1):45–51. doi: 10.1016/0306-4522(90)90118-n. [DOI] [PubMed] [Google Scholar]
  17. Molnár E., Baude A., Richmond S. A., Patel P. B., Somogyi P., McIlhinney R. A. Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit: cellular and subcellular distribution in the rat forebrain. Neuroscience. 1993 Mar;53(2):307–326. doi: 10.1016/0306-4522(93)90198-o. [DOI] [PubMed] [Google Scholar]
  18. Petralia R. S., Wenthold R. J. Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in the rat brain. J Comp Neurol. 1992 Apr 15;318(3):329–354. doi: 10.1002/cne.903180309. [DOI] [PubMed] [Google Scholar]
  19. Represa A., Tremblay E., Ben-Ari Y. Kainate binding sites in the hippocampal mossy fibers: localization and plasticity. Neuroscience. 1987 Mar;20(3):739–748. doi: 10.1016/0306-4522(87)90237-5. [DOI] [PubMed] [Google Scholar]
  20. Seeburg P. H. The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 1993 Sep;16(9):359–365. doi: 10.1016/0166-2236(93)90093-2. [DOI] [PubMed] [Google Scholar]
  21. Smith A. L., McIlhinney R. A. Effects of acromelic acid A on the binding of [3H]-kainic acid and [3H]-AMPA to rat brain synaptic plasma membranes. Br J Pharmacol. 1992 Jan;105(1):83–86. doi: 10.1111/j.1476-5381.1992.tb14214.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Swope S. L., Moss S. J., Blackstone C. D., Huganir R. L. Phosphorylation of ligand-gated ion channels: a possible mode of synaptic plasticity. FASEB J. 1992 May;6(8):2514–2523. [PubMed] [Google Scholar]
  24. Ułas J., Monaghan D. T., Cotman C. W. Kainate receptors in the rat hippocampus: a distribution and time course of changes in response to unilateral lesions of the entorhinal cortex. J Neurosci. 1990 Jul;10(7):2352–2362. doi: 10.1523/JNEUROSCI.10-07-02352.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wenthold R. J., Yokotani N., Doi K., Wada K. Immunochemical characterization of the non-NMDA glutamate receptor using subunit-specific antibodies. Evidence for a hetero-oligomeric structure in rat brain. J Biol Chem. 1992 Jan 5;267(1):501–507. [PubMed] [Google Scholar]
  26. Wisden W., Seeburg P. H. A complex mosaic of high-affinity kainate receptors in rat brain. J Neurosci. 1993 Aug;13(8):3582–3598. doi: 10.1523/JNEUROSCI.13-08-03582.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES