Abstract
The modulation of voltage-dependent calcium channels by hormones and neurotransmitters has important implications for the control of many Ca2+-dependent cellular functions including exocytosis and contractility1–7. We made use of electrophysiological techniques, including whole-cell patch-clamp recordings from dorsal root ganglion (DRG) neurones, to demonstrate a role for GTP-binding proteins (G-proteins) as signal transducers in the noradrenaline- and γ-aminobutyric acid (GABA)-induced inhibition of voltage-dependent calcium channels8–11. This action of the transmitters was blocked by: (1) preincubation of the cells with pertussis toxin (a bacterial exotoxin catalysing ADP-ribosylation of G-proteins12); or (2) intracellular administration of guanosine 5′-O-(2-thiodiphosphate) (GDP-β-S), a non-hydrolysable analogue of GDP that competitively inhibits the binding of GTP to G-proteins13. Our findings provide the first direct demonstration of the G-protein-mediated inhibition of voltage-dependent calcium channels by neurotransmitters. This mode of transmitter action may explain the ability of noradrenaline and GABA to presynaptically inhibit Ca2+-dependent neurosecretion from DRG sensory neurones4,5.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kupferman, I. A. Rev. Neurosci. 2, 447–465 (1979).
Shain, W. & Carpenter, D. O. Int. Rev. Neurobiol. 22, 205–250 (1981).
Dunlap, K. in The Mechanism of Gated Calcium Transport across Biological Membranes (eds Ohnishi, S. T. & Endo, M.) 87–97 (Academic, New York, 1981).
Fischbach, G. D., Dunlap, K., Mudge, A. W. & Leeman, S. in Neurosecretion and Brain Peptides (eds Martin, J. B., Reichlin, S. & Bick, K. L.) 175–188 (Raven, New York, 1981).
Holz, G. G., Kream, R. M. & Dunlap, K. Soc. Neurosci Abstr. 11, 126 (1985).
Holz, G. G., Shefner, S. A. & Anderson, E. G. J. Neurosci. (in the press).
Reuter, H. & Scholz, H. J. Physiol., Lond. 264, 49–62 (1977).
Dunlap, K. & Fischbach, G. J. Physiol., Lond. 317, 519–535 (1981).
Dunlap, K. & Fischbach, G. Nature 276, 837–839 (1978).
Houslay, M. D. Trends biochem. Sci. 9, 39–40 (1984).
Gilman, A. G. Cell 36, 577–579 (1984).
Ui, M. Trends pharmac. Sci. 5, 277–279 (1984).
Eckstein, F., Cassel, D., Levkovitz, H., Lowe, M. & Selinger, Z. J. biol. Chem. 254, 9829–9834 (1979).
Dichter, M. & Fischbach, G. D. J. Physiol., Lond. 267, 281–298 (1977).
Katada, T., Bokoch, G. M., Northup, J. K., Ui, M. & Gilman, A. G. J. biol. Chem. 259, 3568–3577 (1984).
Jakobs, K. H., Aktories, K. & Schultz, G. Adv. Cyclic Nucleotide Res. Protein Phosphor. 17, 135–143 (1984).
Rane, S. G. & Dunlap, K. Proc. natn. Acad. Sci. U.S.A. 83, 184–188 (1986).
Hamill, O., Marty, A., Neher, E., Sakman, B. & Sigworth, F.J. Pflügers Arch. ges. Physiol. 391, 85–100 (1981).
Cassel, D., Eckstein, F., Lowe, M. & Selinger, Z. J. biol. Chem. 254, 9835–9838 (1979).
Jakobs, K. H. Eur. J. Biochem. 132, 125–130 (1983).
Lemos, J. R. & Levitan, I. B. J. gen. Physiol. 83, 269–285 (1984).
Canfield, D. R. & Dunlap, K. Br. J. Pharmac. 82, 557–563 (1984).
Dunlap, K. Br. J. Pharmac. 74, 579–585 (1981).
Sabol, S. L. & Nirenberg, M. J. biol. Chem. 254, 1913–1920 (1979).
Wojcik, W. J. & Neff, N. H. Molec. Pharmac. 25, 24–28 (1984).
Hazeki, O. & Ui, M. J. biol. Chem. 256, 2856–2862 (1981).
Cote, T. E., Frey, E. A. & Sekura, R. D. J. biol. Chem. 259, 8693–8698 (1984).
Forscher, P. & Oxford, G. S. J. gen. Physiol. 85, 743–763 (1985).
Neer, E., Lok, J. & Wolf, L. J. biol. Chem. 259, 14222–14229 (1984).
Sternweis, P. C. & Robishaw, J. D. J. biol. Chem. 259, 13806–13813 (1984).
Nakamura, T. & Ui, M. J. biol. Chem. 260, 3584–3593 (1985).
Bradford, P. G. & Rubin, R. P. FEBS Lett. 183, 317–320 (1985).
Volpi, M. et al. Proc. natn. Acad. Sci. U.S.A. 82, 2708–2712 (1985).
Cockcroft, S. & Comperts, B. Nature 314, 534–536 (1985).
Wallace, M. A. & Fain, J. N. J. biol. Chem. 260, 9527–9530 (1985).
Nishizuka, Y. Nature 308, 693–698 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Holz, G., Rane, S. & Dunlap, K. GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels. Nature 319, 670–672 (1986). https://doi.org/10.1038/319670a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/319670a0
This article is cited by
-
D1 receptors in the anterior cingulate cortex modulate basal mechanical sensitivity threshold and glutamatergic synaptic transmission
Molecular Brain (2020)
-
Presynaptic calcium channels: specialized control of synaptic neurotransmitter release
Nature Reviews Neuroscience (2020)
-
The CatSper channel: a polymodal chemosensor in human sperm
The EMBO Journal (2012)
-
Down-Modulation of Ca2+ Channels by Endogenously Released ATP and Opioids: from the Isolated Chromaffin Cell to the Slice of Adrenal Medullae
Cellular and Molecular Neurobiology (2010)
-
Alternative splicing controls G protein–dependent inhibition of N-type calcium channels in nociceptors
Nature Neuroscience (2007)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.