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