Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1996 Mar 15;491(Pt 3):757–772. doi: 10.1113/jphysiol.1996.sp021255

Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones.

O Garaschuk 1, R Schneggenburger 1, C Schirra 1, F Tempia 1, A Konnerth 1
PMCID: PMC1158816  PMID: 8815209

Abstract

1. The Ca2+ permeability of non-NMDA and NMDA receptor channels was studied using a fluorometric flux measurement approach in somata and dendrites of CA1 pyramidal neurones in rat hippocampal slices. For this purpose, the Ca2+ fraction of the total cation current (named 'fractional Ca2+ current') was measured directly from the change in the Ca(2+)-sensitive fura-2 fluorescence at 380 nm excitation wavelength. 2. The fractional Ca2+ current through the somatic NMDA receptor channels was 10.69 +/- 2.13% (mean +/- S.D.) and that through dendritic receptor channels was 10.70 +/- 1.96%. The fractional Ca2+ current was not dependent on the extracellular Mg2+ concentration and its voltage dependence was in agreement with the Goldman-Hodgkin-Katz current equation. 3. AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) or kainate applications produced small but significant Ca2+ entry. Fractional Ca2+ currents of 0.58 +/- 0.34% were measured for somatic AMPA applications, 0.68 +/- 0.20% for somatic kainate applications, 0.66 +/- 0.25% for dendritic AMPA applications and 0.61 +/- 0.16% for dendritic kainate applications. 4. The expression pattern of glutamate receptor subunits encoding messenger ribonucleic acids (mRNAs) was analysed with the single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) approach applied to CA1 pyramidal neurones. The AMPA receptor subunits GluR-A, GluR-B and GluR-C, and the NMDA receptor subunits NR2A and NR2B were found to be abundantly expressed in all CA1 pyramidal neurones tested. 5. This study establishes the fractional Ca2+ current through somatic and dendritic NMDA and non-NMDA receptor channels in CA1 pyramidal neurones. The dendritic, presumably synaptic, NMDA receptor channels are highly Ca2+ permeable and have a fractional Ca2+ current closely resembling that of somatic extrasynaptic NMDA receptor channels. Both somatic and dendritic non-NMDA receptor channels are of the 'low Ca2+ permeable' type and have a fractional Ca2+ current that is about twenty times smaller than that of NMDA receptor channels.

Full text

PDF
757

Images in this article

Selected References

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

  1. Audinat E., Lambolez B., Rossier J., Crépel F. Activity-dependent regulation of N-methyl-D-aspartate receptor subunit expression in rat cerebellar granule cells. Eur J Neurosci. 1994 Dec 1;6(12):1792–1800. doi: 10.1111/j.1460-9568.1994.tb00572.x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bochet P., Audinat E., Lambolez B., Crépel F., Rossier J., Iino M., Tsuzuki K., Ozawa S. Subunit composition at the single-cell level explains functional properties of a glutamate-gated channel. Neuron. 1994 Feb;12(2):383–388. doi: 10.1016/0896-6273(94)90279-8. [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. Burnashev N., Zhou Z., Neher E., Sakmann B. Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes. J Physiol. 1995 Jun 1;485(Pt 2):403–418. doi: 10.1113/jphysiol.1995.sp020738. [DOI] [PMC free article] [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. Edwards F. A., Konnerth A., Sakmann B., Takahashi T. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflugers Arch. 1989 Sep;414(5):600–612. doi: 10.1007/BF00580998. [DOI] [PubMed] [Google Scholar]
  8. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  9. Hestrin S., Nicoll R. A., Perkel D. J., Sah P. Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J Physiol. 1990 Mar;422:203–225. doi: 10.1113/jphysiol.1990.sp017980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Hume R. I., Dingledine R., Heinemann S. F. Identification of a site in glutamate receptor subunits that controls calcium permeability. Science. 1991 Aug 30;253(5023):1028–1031. doi: 10.1126/science.1653450. [DOI] [PubMed] [Google Scholar]
  12. Iino M., Ozawa S., Tsuzuki K. Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones. J Physiol. 1990 May;424:151–165. doi: 10.1113/jphysiol.1990.sp018060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jahr C. E., Stevens C. F. Calcium permeability of the N-methyl-D-aspartate receptor channel in hippocampal neurons in culture. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11573–11577. doi: 10.1073/pnas.90.24.11573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jonas P., Sakmann B. Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices. J Physiol. 1992 Sep;455:143–171. doi: 10.1113/jphysiol.1992.sp019294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kano M., Garaschuk O., Verkhratsky A., Konnerth A. Ryanodine receptor-mediated intracellular calcium release in rat cerebellar Purkinje neurones. J Physiol. 1995 Aug 15;487(1):1–16. doi: 10.1113/jphysiol.1995.sp020857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Keller B. U., Hollmann M., Heinemann S., Konnerth A. Calcium influx through subunits GluR1/GluR3 of kainate/AMPA receptor channels is regulated by cAMP dependent protein kinase. EMBO J. 1992 Mar;11(3):891–896. doi: 10.1002/j.1460-2075.1992.tb05127.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Keller B. U., Konnerth A., Yaari Y. Patch clamp analysis of excitatory synaptic currents in granule cells of rat hippocampus. J Physiol. 1991 Apr;435:275–293. doi: 10.1113/jphysiol.1991.sp018510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lambolez B., Audinat E., Bochet P., Crépel F., Rossier J. AMPA receptor subunits expressed by single Purkinje cells. Neuron. 1992 Aug;9(2):247–258. doi: 10.1016/0896-6273(92)90164-9. [DOI] [PubMed] [Google Scholar]
  19. Lerma J., Morales M., Ibarz J. M., Somohano F. Rectification properties and Ca2+ permeability of glutamate receptor channels in hippocampal cells. Eur J Neurosci. 1994 Jul 1;6(7):1080–1088. doi: 10.1111/j.1460-9568.1994.tb00605.x. [DOI] [PubMed] [Google Scholar]
  20. Lerma J., Paternain A. V., Naranjo J. R., Mellström B. Functional kainate-selective glutamate receptors in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11688–11692. doi: 10.1073/pnas.90.24.11688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lipton S. A. Prospects for clinically tolerated NMDA antagonists: open-channel blockers and alternative redox states of nitric oxide. Trends Neurosci. 1993 Dec;16(12):527–532. doi: 10.1016/0166-2236(93)90198-u. [DOI] [PubMed] [Google Scholar]
  22. Mayer M. L., Westbrook G. L. Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol. 1987 Dec;394:501–527. doi: 10.1113/jphysiol.1987.sp016883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Moriyoshi K., Masu M., Ishii T., Shigemoto R., Mizuno N., Nakanishi S. Molecular cloning and characterization of the rat NMDA receptor. Nature. 1991 Nov 7;354(6348):31–37. doi: 10.1038/354031a0. [DOI] [PubMed] [Google Scholar]
  25. Neher E., Augustine G. J. Calcium gradients and buffers in bovine chromaffin cells. J Physiol. 1992 May;450:273–301. doi: 10.1113/jphysiol.1992.sp019127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  27. Rogers M., Dani J. A. Comparison of quantitative calcium flux through NMDA, ATP, and ACh receptor channels. Biophys J. 1995 Feb;68(2):501–506. doi: 10.1016/S0006-3495(95)80211-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spruston N., Jonas P., Sakmann B. Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. J Physiol. 1995 Jan 15;482(Pt 2):325–352. doi: 10.1113/jphysiol.1995.sp020521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tempia F., Kano M., Schneggenburger R., Schirra C., Garaschuk O., Plant T., Konnerth A. Fractional calcium current through neuronal AMPA-receptor channels with a low calcium permeability. J Neurosci. 1996 Jan 15;16(2):456–466. doi: 10.1523/JNEUROSCI.16-02-00456.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wisden W., Seeburg P. H. Mammalian ionotropic glutamate receptors. Curr Opin Neurobiol. 1993 Jun;3(3):291–298. doi: 10.1016/0959-4388(93)90120-n. [DOI] [PubMed] [Google Scholar]
  31. Zhou Z., Neher E. Calcium permeability of nicotinic acetylcholine receptor channels in bovine adrenal chromaffin cells. Pflugers Arch. 1993 Dec;425(5-6):511–517. doi: 10.1007/BF00374879. [DOI] [PubMed] [Google Scholar]

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

RESOURCES