Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Direct activation of the ion channel TRPA1 by Ca2+

Nature Neuroscience volume 10, pages 277–279 (2007)Cite this article

Abstract

TRPA1 is an ion channel expressed by nociceptors and activated by irritant compounds such as mustard oil. The endogenous function of TRPA1 has remained unclear, a fact highlighted by ongoing debate over its potential role as a sensor of noxious cold. Here we show that intracellular Ca2+ activates human TRPA1 via an EF-hand domain and that cold sensitivity occurs indirectly (and nonphysiologically) through increased [Ca2+]i during cooling in heterologous systems.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: TRPA1 is activated by intracellular Ca2+.
Figure 2: Mechanisms of Ca2+ activation of TRPA1.

Similar content being viewed by others

References

  1. Jordt, S.E. et al. Nature 427, 260–265 (2004).

    Article  CAS  Google Scholar 

  2. Nagata, K., Duggan, A., Kumar, G. & Garcia-Anoveros, J. J. Neurosci. 25, 4052–4061 (2005).

    Article  CAS  Google Scholar 

  3. Nilius, B. et al. J. Physiol. (Lond.) 567, 35–44 (2005).

    Article  CAS  Google Scholar 

  4. Nilius, B. et al. J. Biol. Chem. 278, 30813–30820 (2003).

    Article  CAS  Google Scholar 

  5. Hofmann, T., Chubanov, V., Gudermann, T. & Montell, C. Curr. Biol. 13, 1153–1158 (2003).

    Article  CAS  Google Scholar 

  6. Zhu, M.X. Pflugers Arch. 451, 105–115 (2005).

    Article  CAS  Google Scholar 

  7. Nilius, B. et al. J. Biol. Chem. 280, 6423–6433 (2005).

    Article  CAS  Google Scholar 

  8. Nelson, M.R. & Chazin, W.J. Biometals 11, 297–318 (1998).

    Article  CAS  Google Scholar 

  9. Clapham, D.E. Nature 426, 517–524 (2003).

    Article  CAS  Google Scholar 

  10. Story, G.M. et al. Cell 112, 819–829 (2003).

    Article  CAS  Google Scholar 

  11. Bautista, D.M. et al. Cell 124, 1269–1282 (2006).

    Article  CAS  Google Scholar 

  12. Kwan, K.Y. et al. Neuron 50, 277–289 (2006).

    Article  CAS  Google Scholar 

  13. Talavera, K. et al. Nature 438, 1022–1025 (2005).

    Article  CAS  Google Scholar 

  14. Reid, G. Pflugers Arch. 451, 250–263 (2005).

    Article  CAS  Google Scholar 

  15. Bandell, M. et al. Neuron 41, 849–857 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J.P. Adelman (Oregon Health & Science University) and S.E. Jordt (Yale University) for providing CaM1,2,3,4 and human TRPA1 clones, respectively, and C. Stein and G. Lewin for comments. Supported by Deutsche Forschungsgemeinschaft grants HE-4483 and KFO100.

Author information

Author notes

  1. Sandra Zurborg and Brian Yurgionas: These authors contributed equally to this work.

Authors and Affiliations

  1. Klinik für Anaesthesiologie und operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, D-12200, Germany

    Sandra Zurborg, Brian Yurgionas, Julia A Jira, Ombretta Caspani & Paul A Heppenstall

Authors
  1. Sandra Zurborg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian Yurgionas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julia A Jira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ombretta Caspani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul A Heppenstall
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.Z. and B.Y. conducted the electrophysiology and Ca2+ imaging experiments. J.A.J. conducted the CaM experiments, O.C. made the cell line, and S.Z., B.Y., J.A.J. and P.A.H. analyzed the data. P.A.H. wrote the manuscript.

Corresponding author

Correspondence to Paul A Heppenstall.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Current traces of TRPA1 activation by Ca2+. (PDF 78 kb)

Supplementary Fig. 2

Calmodulin does not regulate activation of TRPA1 by Ca2+. (PDF 73 kb)

Supplementary Fig. 3

Cooling does not shift voltage dependent activation of TRPA1. (PDF 115 kb)

Supplementary Methods (PDF 92 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zurborg, S., Yurgionas, B., Jira, J. et al. Direct activation of the ion channel TRPA1 by Ca2+. Nat Neurosci 10, 277–279 (2007). https://doi.org/10.1038/nn1843

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1843

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing