Abstract
ACETYLCHOLINE activates inwardly rectifying potassium channels (Ik.ACh) in the heart1 through muscarinic receptor binding and activation of pertussis-toxin-sensitive G proteins2,3. Experiments showing that only the βγ-subunit (Gβγ) activates IK.ACH (ref. 4) were challenged by reports that only the activated α-subunit (Gα) was effective5. Here we examine IK.ACh regulation using purified brain and recombinant G-protein subunits. Six recombinant Gβγ-subunits activated IK.ACh with apparent half-maximal activation concentrations of 3-30 nM. Activation of IK.ACh by recombinant Gα-GTPγS was observed, but this was probably due to release of GTPγS from the protein. Importantly, IK.ACh activity elicited by GTPγS was inhibited by purified brain and recombinant Gα-GDP, suggesting that native Gβγ plays a major role in this pathway. We conclude that Gβγ is a primary regulator of IK.ACh activity.
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
Sakmann, B., Norna, A. & Trautwein, W. Nature 303, 250–253 (1983).
Pfaffinger, P. J., Martin, J. M., Hunter, D. D., Nathanson, N. M. & Hille, B. Nature 317, 536–538 (1985).
Breitwieser, G. E. & Szabo, G. Nature 317, 538–540 (1985).
Logothetis, D. E., Kurachi, Y., Galper, J., Neer, E. J. & Clapham, D. E. Nature 325, 321–326 (1987).
Codina, J., Yatani, A., Grenet, D., Brown, A. M. & Birnbaumer, L. Science 236, 442–445 (1987).
Clapham, D. E. & Neer, E. J. Nature 365, 403–406 (1993).
In̄iguez-Lluhi, J., Simon, M. I., Robishaw, J. D. & Gilman, A. G. J. biol. Chem. 267, 23409–23417 (1992).
Ueda, N. et al. J. biol. Chem. (in the press).
Muntz, K. H., Sternweis, P. C., Gilman, A. G. & Mumby, S. M. Molec. biol. Cell 3, 49–61 (1992)
Mattera, R. et al. J. biol. Chem. 264, 465–471 (1989).
Taussig, R., Quarmby, L. M. & Gilman, A. G. Science 268, 9–12 (1993).
Kubo, Y., Reuveny, E., Slesinger, P. A., Jan, Y. N. & Jan, L. Y. Nature 364, 802–806 (1993).
Dascal, N. et al. Proc. natn. Acad. Sci. U.S.A. 90, 10235–10239 (1993).
Sternweis, P. C. & Robishaw, J. D. J. biol. Chem. 259, 13806–13813 (1984).
Roof, D. J., Applebury, M. L. & Sternweis, P. C. J. biol. Chem. 260. 16242–16249 (1985).
Pang, I.-H. & Sternweis, P. C. Proc. natn. Acad. Sci. U.S.A. 86, 7814–7818 (1989).
Linder, M. E. et al. J. biol. Chem. 266, 4654–4659 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wickman, K., Iñiguez-Lluhi, J., Davenport, P. et al. Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel. Nature 368, 255–257 (1994). https://doi.org/10.1038/368255a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/368255a0
This article is cited by
-
A constricted opening in Kir channels does not impede potassium conduction
Nature Communications (2020)
-
Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel
Nature Communications (2019)
-
Targeting G protein-coupled receptor signalling by blocking G proteins
Nature Reviews Drug Discovery (2018)
-
Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
Scientific Reports (2018)
-
The Effect of Histamine on Inward and Outward Currents in Mouse Retinal Amacrine Cells
Cellular and Molecular Neurobiology (2018)
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.