Abstract
THE most commonly used signal transduction pathway for receptor-mediated N-type Ca2+-channel modulation involves activation of a heterotrimeric G protein to produce voltage-dependent inhibition1. Although it is widely assumed that Gα mediates this effect, experiments to address this hypothesis directly are lacking. Here I show that transient overexpression of Gβγ in sympathetic neurons mimics and occludes the voltage-dependent Ca2+ channel modulation produced by noradrenaline (NA). Conversely, over-expression of Gα produces minimal effects on basal Ca2+ channel behaviour but attenuates NA-mediated inhibition in a manner consistent with the buffering of Gβγ. These observations indicate that it is Gβγ, and not Gα, that mediates voltage-dependent inhibition of N-type Ca2+ channels. The identification of Gβγ as the mediator of this pathway has broad implications as G-protein-coupled receptors, many of which are implicated in disease or are targets of therapeutic agents, couple to N-type Ca2+ channels2 and may modulate synaptic transmission by this mechanism3,4.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hille, B. Trends Neurosci. 17, 531–536 (1994).
Anwyl, R. Brain Res. Rev. 16, 265–281 (1991).
Miller, R. FASEB J. 4, 3291–3299 (1990).
Dunlap, K., Luebke, J. & Turner, T. Trends Neurosci. 18, 89–98 (1995).
Plummer, M. R., Rittenhouse, A., Kanevsky, M. & Hess, P. J. Neurosci. 11, 2339–2348 (1991).
Regan, L. J., Sah, D. W. Y. & Bean, B. P. Neuron 6, 269–280 (1991).
Diversé-Pierluissi, M., Goldsmith, P. K. & Dunlap, K. Neuron 14, 191–200 (1995).
Schofield, G. G. Eur. J. Pharmac. 180, 37–47 (1990).
Strittmatter, S. M., Fishman, M. C. & Zhu, X.-P. J. Neurosci. 14, 2327–2338 (1994).
Caulfield, M. P. et al. J. Physiol., Lond. 477, 415–422 (1994).
Bean, B. Nature 340, 153–156 (1989).
Grassi, F. & Lux, H. D. Neurosci. Lett. 105, 113–119 (1989).
Elmslie, K. S., Zhou, W. & Jones, S. W. Neuron 5, 75–80 (1990).
Slepak, V. Z., Katz, A. & Simon, M. I. J. biol. Chem. 270, 4037–4041 (1995).
Slepak, V. Z., Wilkie, T. M. & Simon, M. I. J. biol. Chem. 268, 1414–1423 (1993).
Slepak, V. Z. et al. J. biol. Chem. 268, 21889–21894 (1993).
Masters, S. B. et al. J. biol. Chem. 264, 15467–15474 (1989).
Ikeda, S. R. J. Physiol., Lond. 439, 181–214 (1991).
Clapham, D. E. & Neer, E. J. Nature 365, 403–406 (1993).
Müller, S. & Lohse, M. J. Biochem. Soc. Trans. 23, 141–148 (1995).
Chen, H. et al. Science 268, 1166–1169 (1995).
Pragnell, M. et al. Nature 368, 67–70 (1994).
Campbell, V., Berrow, N. S., Fitzgerald, E. M., Brickley, K. & Dolphin, A. C. J. Physiol., Lond. 485, 365–372 (1995).
Roche, J. P., Anantharam, V. & Treistman, S. N. FEBS Lett. 371, 43–46 (1995).
Bourinet, E. et al. Soc. Neurosci. Abstr. 21, 515 (1995).
Mintz, I. & Bean, B. P. Neuron 10, 889–898 (1993).
Logothetis, D. E., Kurachi, Y., Galper, J., Neer, E. J. & Clapham, D. E. Nature 325, 321–326 (1987).
Zhu, Y. & Ikeda, S. R. Neuron 13, 657–669 (1994).
Ikeda, S. R., Lovinger, D. M., McCool, B. A. & Lewis, D. L. Neuron 14, 1029–1038 (1995).
Heim, R., Cubitt, A. B. & Tsien, R. Y. Nature 373, 663–664 (1995).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ikeda, S. Voltage-dependent modulation of N-type calcium channels by G-protein β γsubunits. Nature 380, 255–258 (1996). https://doi.org/10.1038/380255a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/380255a0
- Springer Nature Limited
This article is cited by
-
Involvement of Ca2+ in Signaling Mechanisms Mediating Muscarinic Inhibition of M Currents in Sympathetic Neurons
Cellular and Molecular Neurobiology (2023)
-
How changes in dopamine D2 receptor levels alter striatal circuit function and motivation
Molecular Psychiatry (2022)
-
Optogenetics at the presynapse
Nature Neuroscience (2022)
-
Local modulation by presynaptic receptors controls neuronal communication and behaviour
Nature Reviews Neuroscience (2022)