Mechanisms Underlying Excitatory Amino Acid-Evoked Calcium Entry in Cultured Neurons from the Embryonic Rat Spinal Cord

  • Amy B. MacDermott
  • David B. Reichling
  • Ottavio Arancio
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 268)


Intracellular calcium is a ubiquitous and potent regulator of many cellular enzymes, channels, pumps, and structural elements. To perform such a variety of functions, the concentration of intracellular calcium ions ([Ca2+]i) must be carefully regulated. In vertebrate neurons, resting calcium levels are generally fixed between 5 and 10x10-8 M. However in an intact nervous system, neurons are seldom at rest and [Ca2+]i can vary with both time and spatial distribution within a neuron. Fluctuations of [Ca2+]i over orders of magnitude have been recorded from neurons in slices and in culture, in the absence of any external stimulus (Tank et al, 1988, Connor et al, 1987, Womack et al, 1988). These calcium transients can be driven by intrinsically-generated membrane oscillations or by synaptic activity. The studies described in this chapter address some of the mechanisms by which excitatory amino acid-mediated synaptic transmission might produce transient elevations of [Ca2+]i.


NMDA Receptor Excitatory Amino Acid Calcium Entry Excitatory Amino Acid Receptor NMDA Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arancio, O. and MacDermott, A. B., 1989, Differential distribution of excitatory amino acid receptors on embryonic rat spinal cord neurons in culture. In preparation.Google Scholar
  2. Arancio, O., Murase, K., Yoshimura, M, and MacDermott, A. B., 1989, Heterogeneous distribution of excitatory amino acid receptors on postnatal neurons acutely dissociated from rat dorsal horn, Neuroscience Abstracts, 15: 943.Google Scholar
  3. Brown, A. G., 1981, Organization in the Spinal Cord, Springer-Verlag, New York.CrossRefGoogle Scholar
  4. Collingridge, G. L., Herron, C. E. and Lester, R. A. J., 1988, Synaptic activation of N-methyl-D aspartate receptors in the schaffer collateral-commissural pathway of rat hippocampus, J. Physiol., 399: 283.Google Scholar
  5. Connor, J. A., Tseng, H-Y., and Hockberger, P. E., 1987, Depolarization-and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures,J. Neurosci., 7: 1384.PubMedGoogle Scholar
  6. Dale, N. and Roberts, A., 1985, Dual-component amino-acid-mediated synaptic potentials: Excitatory drive for swimming in Xenopus embryos, J. Physiol., 363: 35.PubMedGoogle Scholar
  7. Davies, J. and Watkins, J. C., 1979, Selective antagonism of amino acid-induced and synaptic excitation in the cat spinal cord. J. Physiol., 297: 621.Google Scholar
  8. De Biasi, S. and Rustioni, A., 1988, Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord, Proc. Natl. Acad. Sci., 85: 7820.Google Scholar
  9. Flatman, J.A., Schwindt, P.C. and Crill, W.E. (1986) The induction and modification of voltage sensitive responses in cat neocortical neurons by N-methyl-D-aspartate. Brain Res. 363: 62.PubMedCrossRefGoogle Scholar
  10. Forsythe, I. A. and Westbrook, G. L., 1988, Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on cultured mouse central neuronis, J. Physiol., 396: 515.Google Scholar
  11. Greenamyre, J. T., Young, A. 3., and Penney, J. B., 1984, Quantitative autoradiographic distribution of L-[3H] glutamate binding sites in rat central nervous system. J. Neurosci., 4: 2133.Google Scholar
  12. Grillner, S. and Wallen, P., 1985, The ionic mechanisms underlying N-methyl-D-aspartate receptor-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion, Neurosci. Lett., 60: 289.Google Scholar
  13. Grynkiewicz, G., Poenie, M. and Tsien, R. Y., 1985, A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260: 3440.Google Scholar
  14. Heyer, E. J., MacDonald, R. L., Bergey, G. K., and Nelson, P. G., 1981, Calcium-dependent action potentials in mouse spinal cord neurons in culture, Brain Res., 220: 408.Google Scholar
  15. Huang, L-Y. M., 1989, Calcium channels in isolated rat dorsal horn neurones, including labelled spinothalamic and trigeminal cells, J. Physiol., 411: 161Google Scholar
  16. Huettner, J. E., and Baughman, R. W., 1988, The pharmacology of synapses formed by identified corticocollicular neurons in primary cultures of rat visual cortex, J. Neurosci., 8: 160Google Scholar
  17. Jack, J. J. B., Redman, S. J., and Wong, K., 1981, The components of synaptic potentials evoked in cat spinal notoneurones by impulses in single group Ia afferents, J. Physiol., 321: 65.Google Scholar
  18. Jahr, C. E. and lessen, T. M., 1985, Synaptic transmission between dorsl horn neurons in culture: antagonism of monosynaptic EPSPs and glutamate excitation by kynurenate, J. Neurosci., 5: 2281.PubMedGoogle Scholar
  19. Johnson, J. W. and Ascher, P., 1987, Glycine potentiates the NMDA response in cultured mouse brain neurons, Nature, 325: 529.PubMedCrossRefGoogle Scholar
  20. Jones, K. A. and Baughman, R. W., 1988, NMDA- and non-NMDA-receptor components of excitatory synaptic potentials recorded from cells in layer V of rat visual cortex, J. Neurosci., 8: 3522.Google Scholar
  21. Kleckner, N. K. and Dingledine, R., 1989, Glycine is required for activation of NMDA receptors in Xenopus oocytes injected with rat brain mRNA, Science, 241: 835.CrossRefGoogle Scholar
  22. Kudo, Y. and Ogura, A., 1986, Glutamtate-induced increase in intracellular Cat+ concentration in isolated hippocampal neurones, Br. J. Pharmac., 89: 191.Google Scholar
  23. Llinas, R. R., 1988, The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function, Science, 242: 1654.PubMedCrossRefGoogle Scholar
  24. Llinas, R. and Sugimori, M., 1980, Electrophysiological properites of in vitro Purkinje cell dendrites in mammalian cerebellar slices, J. Physiol., 305: 197.Google Scholar
  25. MacDermott, A. B., Mayer, M. L., Westbrook, G. L., Smith, S. J., Barker, J. L., 1986, NMDA receptor activation elevates cytoplasmic calcium in cultured spinal cord neurones, Nature, 321: 519.PubMedCrossRefGoogle Scholar
  26. MacDermott, A. B. and Dale, N., 1987, Receptors, ion channels and synaptic potentials underlying the integrative actions of excitatory amino acids, TINS, 10: 280.Google Scholar
  27. MacDonald, J. F. and Wojtowicz, J. M., 1982, The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture, Can. J. Physiol. Pharmacol., 60: 282.Google Scholar
  28. Mayer, M. L., MacDermott, A. B., Westbrook, G. L., Smith, S. J., and Barker, J. L., 1987, Agonistand voltage-gated calcium entry in cultured mouse spinal cord neurons under voltage clamp measured using arsenazo III, J. Neurosci., 7: 3230.Google Scholar
  29. Mayer, M. L., Westbrook, G. L. and Guthrie, P. B., 1984, Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones, Nature 309: 261.PubMedCrossRefGoogle Scholar
  30. Mayer, M. L. and Westbrook, G. L., 1987, The physiology of excitatory amino acids in the vertebrate central nervous system, Prog. Neurobiol., 28: 276.Google Scholar
  31. Monaghan, D. T. and Cotman, C. W., 1985, Distribution of N-mehtyl-D-aspartate-sensitive 1-(3H]Glutamate-binding sites in rat brain, J. Neurosci., 5: 2909.Google Scholar
  32. Murase, K. and Randic, M., 1983, Electrophysiological properties of rat spinal dorsal horn neurones in vitro: calcium-dependent action potentials, J. Physiol., 334: 141.Google Scholar
  33. Murphy, S. N. and Miller, R. J., 1989, Regulation of Cat+ influx into striatal neurons by kainic acid, J. Pharmacol. Exp. Ther., 249: 184.Google Scholar
  34. Murphy, S. N., Thayer, S. A., and Miller, R. J., 1987, The effects of excitatory amino acids on intracellular calcium in single mouse striatal neurons in vitro, J. Neurosci., 7: 4145.Google Scholar
  35. Neale, E. A., Nelson, P. G., MacDonald, R. L., Christian, C. N., and Bowers, L. M., 1983, Synaptic interactions between mammalian central neurons in cell culture. III Morphological correlates of quantal synaptic transmission, J. Neurophysiol., 49: 1459.Google Scholar
  36. Nowak, L., Bregestovski, P., Ascher, P., Herbert, A.and Proshiantz, A., 1984, Magnesium gates glutamate-activated channels in mouse central neurones, Nature 307: 462.Google Scholar
  37. O’Brien, R. J. and Fischbach, G. D., 1986, Characterization of excitatory amino acid receptors expressed by embryonic chick motoneurons in vitro, J. Neurosci., 6: 3275.Google Scholar
  38. O’Brien, R. J. and Fischbach, G. D., 1986, Modulation of embryonic chich motoneuron glutamate sensitivity by interneurons and agonists. J. Neurosci., 6: 3290.Google Scholar
  39. Ransom, B. R., Bullock, P. N., and Nelson, P. G., 1977, Mouse spinal cord in cell culture. III. Neuronal chemosensitivity and its relationship to synaptic activity, J. Neurophysiol., 40: 1163.Google Scholar
  40. Schneider, S. P. and Perl, E. R., 1985, Selective excitation of neurons in the mammalian spinal dorsal horn by aspartate and glutamate in vitro: correlation with location and excitatory input, Brain Res., 360: 339.Google Scholar
  41. Tank, D. W., Sugimori, M., Connor, J. A., and Llinas, R. R., 1988, Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice, Science, 242: 773.PubMedCrossRefGoogle Scholar
  42. Thomson, A. M., 1986, A magnesium-sensitive post-synaptic potential in rat cerebral cortex resembles neuronal responses to N-methylaspartate, J. Physiol., 370: 531.Google Scholar
  43. Trussell, L. O., Thio, L. L., Zorumski, C. F., and Fischbach, G. D., 1988, Rapid desensitization of glutamate receptors in vertebrate central neurons, Proc. Natl. Acad. Sci., 85: 4562.CrossRefGoogle Scholar
  44. Watkins, J.C. and Evans, R.H. (1981) Excitatory amino acid transmitters. Ann. Rev. Pharmacol.Toxicol. 21 165–204.CrossRefGoogle Scholar
  45. Westbrook, G. L. and Mayer, M. L., 1984, Glutamate currents in mammalian spinal neurons: resolution of a paradox, Brain Res., 301: 375.Google Scholar
  46. Womack, M. D., MacDermott, A. B., and Jesse’’, T. M., 1988, Sensory transmitters regulate intracellular calcium in dorsal horn neurons, Nature, 334: 351.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Amy B. MacDermott
    • 1
  • David B. Reichling
    • 1
  • Ottavio Arancio
    • 1
  1. 1.Department of Physiology and Cellular Biophysics and the Center for Neurobiology and BehaviorColumbia UniversityNew YorkUSA

Personalised recommendations