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Bimodal effects of cinnamaldehyde and camphor on mouse TRPA1

  • Ion Channels, Receptors and Transporters
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

TRPA1 is a nonselective cation channel activated by a wide variety of noxious chemicals. Intriguingly, several TRPA1 modulators induce a bimodal effect, activating the channel at micromolar concentrations and inhibiting it at higher concentrations. Here we report the bimodal action of cinnamaldehyde (CA) and camphor, which are thus far reported as agonist and antagonist of TRPA1, respectively. Whole-cell patch-clamp experiments in TRPA1-expressing CHO cells revealed that, as previously reported, extracellular application of 100 μM CA strongly stimulates TRPA1 currents. However, subsequent application of 3 mM CA induced fast and reversible current inhibition. Application of 3 mM CA in basal conditions induced a rather small current increase, followed by current inhibition and a dramatic rebound of current amplitude upon washout. These observations are reminiscent of the effects of TRPA1 modulators having bimodal effects, e.g., menthol and nicotine. In line with previous reports, extracellular application of 1 mM camphor induced a decrease of basal TRPA1 currents. However, the current amplitude showed a significant overshoot upon washout. On the other hand, application of 100 μM camphor induced a 3-fold increase of the basal current amplitude measured at −75 mV. The bimodal effects of CA and camphor on TRPA1 were also observed in microfluorimetric measurements of intracellular Ca2+ in intact TRPA1-expressing CHO cells and in primary cultures of mouse dorsal root ganglion neurons. These findings are essential for the understanding of the complex sensory properties of these compounds, as well as their utility when used to study the pathophysiological relevance of TRPA1.

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Authors and Affiliations

  1. Laboratory for Ion Channel Research and TRP Channel Research Platform, Department of Cellular and Molecular Medicine, KU Leuven, 3000, Leuven, Belgium

    Yeranddy A. Alpizar, Maarten Gees, Alicia Sanchez, Aurelia Apetrei, Thomas Voets, Bernd Nilius & Karel Talavera

  2. Laboratory of Molecular Biophysics and Medical Physics, Department of Physics, “Alexandru I. Cuza” University, 700506, Iasi, Romania

    Aurelia Apetrei

  3. Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, 3000, Leuven, Belgium

    Karel Talavera

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  1. Yeranddy A. Alpizar
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  2. Maarten Gees
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  3. Alicia Sanchez
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Correspondence to Karel Talavera.

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Alpizar, Y.A., Gees, M., Sanchez, A. et al. Bimodal effects of cinnamaldehyde and camphor on mouse TRPA1. Pflugers Arch - Eur J Physiol 465, 853–864 (2013). https://doi.org/10.1007/s00424-012-1204-x

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