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Modulation of Ca2+ channels βγ G-protein py subunits

Naturevolume 380pages258262 (1996) | Download Citation

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  • An Erratum to this article was published on 09 May 1996

Abstract

CALCIUM ions entering cells through voltage-gated Ca2+ channels initiate rapid release of neurotransmitters and secretion of hormones. Ca2+ currents can be inhibited in many cell types by neurotransmitters acting through G proteins via a membrane-delimited pathway independently of soluble intracellular messengers1–4. Inhibition is typically caused by a positive shift in the voltage dependence and a slowing of channel activation and is relieved by strong depolarization resulting in facilitation of Ca2+currents1,4–6. This pathway regulates the activity of N-type and P/ Q-type Ca2+ channels1,2,7, which are localized in presynaptic terminals8,9 and participate in neurotransmitter release10–13. Synaptic transmission is inhibited by neurotransmitters through this mechanism1,4. G-protein a subunits confer specificity in receptor coupling1–4,14–17, but it is not known whether the Gα or Gβγ subunits are responsible for modulation of Ca2+channels. Here we report that Gβγ subunits can modulate Ca2+ channels. Transfection of Gβγ into cells expressing P/Q-type Ca2+ channels induces modulation like that caused by activation of G protein-coupled receptors, but Gα subunits do not. Similarly, injection or expression of Gβγ subunits in sympathetic ganglion neurons induces facilitation and occludes modulation of N-type channels by noradrenaline, but Gα subunits do not. In both cases, the Gγ subunit is ineffective by itself, but overexpression of exogenous Gβ subunits is sufficient to cause channel modulation.

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References

  1. 1

    Hille, B. Trends Neurosci. 17, 531–536 (1994).

  2. 2

    Hescheler, J. & Schultz, G. Curr. Opin. Neurobiol. 3, 360–367 (1993).

  3. 3

    Wickman, K. D. & Clapham, D. E. Curr. Biol. 5, 278–285 (1995).

  4. 4

    Dolphin, A. C. Expl. Physiol. 80, 1–36 (1995).

  5. 5

    Marchetti, C., Carbone, E. & Lux, H. D. Pflügers Arch. 406, 104–111 (1986).

  6. 6

    Bean, B. P. Nature 340, 153–156 (1989).

  7. 7

    Mintz, I. M. & Bean, B. P. Neuron 10, 889–898 (1993).

  8. 8

    Robitaille, R., Adler, E. M. & Charlton, M. P. Neuron 5, 773–779 (1990).

  9. 9

    Westenbroek, R. E. et al. J. Neurosci. 15, 6403–6418 (1995).

  10. 10

    Hirning, L. D. et al. Science 239, 57–61 (1988).

  11. 11

    Wheeler, D. B., Randall, A. & Tsien, R. W. Science 264, 107–111 (1994).

  12. 12

    Luebke, J. I., Dunlap, K. & Turner, T. J. Neuron 11, 895–902 (1993).

  13. 13

    Takahashi, T. & Momiyama, A. Nature 366, 156–158 (1993).

  14. 14

    Hescheler, J., Rosenthal, W., Trautwein, W. & Schultz, G. Nature 325, 445–446 (1987).

  15. 15

    Wilk-Blaszczak, M. A., Singer, W. D., Gutowski, S., Sternweis, P. C. & Belardetti, F. Neuron 13, 1215–1224 (1994).

  16. 16

    Zhu, Y. & Ikeda, S. R. Neuron 13, 657–669 (1994).

  17. 17

    Diversé-Pierluissi, M., Goldsmith, P. K. & Dunlap, K. Neuron 14, 191–200 (1995).

  18. 18

    Stea, A. et al. Proc. natn. Acad. Sci. U.S.A. 91, 10576–10580 (1994).

  19. 19

    Ellis, S. B. et al. Science 241, 1661–1664 (1988).

  20. 20

    Clapham, D. E. & Neer, E. J. Nature 365, 403–406 (1993).

  21. 21

    Hepler, J. R. & Gilman, A. G. Trends biol. Sci. 17, 383–387 (1992).

  22. 22

    Breitwieser, G. E. & Szabo, G. Nature 317, 538–540 (1985).

  23. 23

    Pfaffinger, P. J., Martin, J. M., Hunter, D. D., Nathanson, N. M. & Hille, B. Nature 317, 536–538 (1985).

  24. 24

    Reuveny, E. et al. Nature 370, 143–146 (1994).

  25. 25

    Kofuji, P., Davidson, N. & Lester, H. A. Proc. natn. Acad. Sci. U.S.A. 92, 6542–6546 (1995).

  26. 26

    Wickman, K. D. et al. Nature 368, 255–257 (1994).

  27. 27

    Chen, J. et al. Science 268, 1166–1169 (1995).

  28. 28

    Hockerman, G. H., Johnson, B. D., Scheuer, T. & Catterall, W. A. J. biol. Chem. 270, 22119–22122 (1995).

  29. 29

    Bernheim, L., Beech, D. J. & Hille, B. Neuron 6, 859–867 (1991).

  30. 30

    Shapiro, M. S., Wollmuth, L. P. & Hille, B. J. Neurosci. 14, 7109–7116 (1994).

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Affiliations

  1. Department of Pharmacology, University of Washington, Seattle, Washington, 98195, USA

    • Stefan Herlitze
    • , Todd Scheuer
    •  & William A. Catterall
  2. Department of Physiology and Biophysics, University of Washington, Seattle, Washington, 98195, USA

    • David E. Garcia
    • , Ken Mackie
    •  & Bertil Hille
  3. Department of Anesthesiology, University of Washington, Seattle, Washington, 98195, USA

    • Ken Mackie
  4. Department of Physiology, Faculty of Medicine, UNAM, CP04510, Mexico City D.F., Mexico

    • David E. Garcia

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https://doi.org/10.1038/380258a0

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