Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission (original) (raw)

Nature volume 361, pages 165–168 (1993)Cite this article

Abstract

FAST synaptic transmission in the central nervous system can be modulated by neurotransmitters and second-messenger pathways. For example, transmission at glutamatergic synapses can be depressed by the metabotropic glutamate receptor1,2, providing autoreceptor-mediated negative feedback. Metabotropic glutamate receptor inhibition of Ca2+ channels may contribute to this pathway3–6. In contrast, stimulation of protein kinase C can enhance excitatory synaptic transmission7, whereas both depression and enhancement of Ca2+ current have been reported8. Here we show that in hippocampal CA3 and cortical pyramidal neurons, activation of protein kinase C enhances current through N-type Ca2+ channels and, in addition, dramatically reduces G protein-dependent inhibition of these same channels by the meta-botropic glutamate receptor. In parallel experiments on fast excitatory transmission at corticostriatal synapses, kinase C activators were similarly found to reduce the inhibitory effect produced by stimulation of the metabotropic glutamate receptor. The results show that second-to-second control of Ca2+ channels by the metabotropic glutamate receptor can itself be modulated on a slower timescale by protein kinase C. These mechanisms may be used in the control of fast excitatory synaptic transmission.

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References

  1. Lovinger, D. M. Neurosci. Lett 129, 17–21 (1991).
    Article CAS Google Scholar
  2. Baskys, A. & Malenka, R. C. J. Physiol., Lond. 444, 687–701 (1991).
    Article CAS Google Scholar
  3. Lester, R. A. & Jahr, C. E. Neuron 4, 741–749 (1990).
    Article CAS Google Scholar
  4. Swartz, K. J. & Bean, B. P. J. Neurosci. 12, 4358–4371 (1992).
    Article CAS Google Scholar
  5. Sayer, R. J., Schwindt, P. C. & Crill, W. E. J. Neurophysiol. 68, 833–842 (1992).
    Article CAS Google Scholar
  6. Sahara, Y. & Westbrook, G. L. Soc. Neurosci. 17, 1168 (1991).
    Google Scholar
  7. Malenka, R. C., Madison, D. V. & Nicoll, R. A. Nature 321, 175–177 (1986).
    Article ADS CAS Google Scholar
  8. Anwyl, R. Brain Res. Rev. 16, 265–281 (1991).
    Article CAS Google Scholar
  9. Palmer, E. et al. Eur. J. Pharmac. 166, 585–587 (1988).
    Article Google Scholar
  10. Irving, A. J. et. al. Eur. J. Pharmac. 186, 363–365 (1990).
    Article CAS Google Scholar
  11. House, C. & Kemp, B. E. Science 238, 1726–1728 (1987).
    Article ADS CAS Google Scholar
  12. Olivera, B. M. et al. Science 230, 1338–1343 (1985).
    Article ADS CAS Google Scholar
  13. Plummer, M. R., Logothetis, D. E. & Hess, P. Neuron 2, 1453–1463 (1989).
    Article CAS Google Scholar
  14. Aosaki, T. & Kasai, H. Pflügers Arch. 414, 150–156 (1989).
    Article CAS Google Scholar
  15. Regan, L. J., San, D. W. Y. & Bean, B. P. Neuron 6, 269–280 (1991).
    Article CAS Google Scholar
  16. Lipscombe, D., Bley, K. & Tsien, R. W. Soc. Neurosci. 14, 153 (1988).
    Google Scholar
  17. Madison, D. V. Soc. Neurosci. 15, 16 (1989).
    Google Scholar
  18. O'Dell, T. J. & Alger, B. E. J. Physiol., Lond. 436, 739–767 (1991).
    Article CAS Google Scholar
  19. Hirning, L. D. et al. Science 239, 57–61 (1988).
    Article ADS CAS Google Scholar
  20. Kamiya, H., Sawada, S. & Yamamoto, C. Neurosci. Lett. 91, 84–88 (1988).
    Article CAS Google Scholar
  21. Horne, A. L. & Kemp, J. A. Br. J. Pharmac. 103, 1733–1739.
  22. Cordingley, G. E. & Weight, F. F. Br. J. Pharmac. 88, 847–856 (1986).
    Article CAS Google Scholar
  23. North, R. A. Br. J. Pharmac. 98, 13–28 (1989).
    Article CAS Google Scholar
  24. Scholz, K. P. & Miller, R. J. Neuron 8, 1139–1150 (1992).
    Article CAS Google Scholar
  25. Dutar, P. & Nicoll, R. A. Neuron 1, 585–591 (1988).
    Article CAS Google Scholar
  26. Thompson, S. M., Haas, H. L. & Gahwiler, B. H. J. Physiol., Lond. 451, 347–363 (1992).
    Article CAS Google Scholar
  27. Leeb-Lundberg, L. M. F. et al. Proc. natn. Acad. Sci. U.S.A. 82, 5651–5655 (1985).
    Article ADS CAS Google Scholar
  28. Pollock, W. K. & MacIntyre, D. E. Biochem. J. 234, 67–73 (1986).
    Article CAS Google Scholar
  29. Schoepp, D. D. & Johnson, B. G. Biochem. Pharmac. 37, 4299–4305 (1988).
    Article CAS Google Scholar
  30. Aramori, I. & Nakanishi, S. Neuron 8, 757–765 (1992).
    Article CAS Google Scholar
  31. Katada, T. et al. Eur. J. Biochem. 151, 431–437 (1985).
    Article CAS Google Scholar
  32. Bollag, G. E. et al. Proc. natn. Acad. Sci. U.S.A. 83, 5822–5824 (1986).
    Article ADS CAS Google Scholar
  33. Bosma, M. M. & Hille, B. Proc. natn. Acad. Sci. U.S.A. 86, 2943–2947 (1989).
    Article ADS CAS Google Scholar
  34. Rane, S. G. et al. Neuron 3, 239–245 (1989).
    Article CAS Google Scholar
  35. Hamill, O. P. et al. Pflügers Arch. 391, 85–100 (1981).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Department of Neurobiology, Harvard Medical School, Boston, Massachussetts, 02115, USA
    Kenton J. Swartz & Bruce P. Bean
  2. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA
    Andrew Merritt & David M. Lovinger

Authors

  1. Kenton J. Swartz
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  2. Andrew Merritt
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  3. Bruce P. Bean
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  4. David M. Lovinger
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Swartz, K., Merritt, A., Bean, B. et al. Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission.Nature 361, 165–168 (1993). https://doi.org/10.1038/361165a0

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