Functional expression of TRPM8 and TRPA1 channels in rat odontoblasts

PLoS One. 2013 Dec 16;8(12):e82233. doi: 10.1371/journal.pone.0082233. eCollection 2013.


Odontoblasts produce dentin during development, throughout life, and in response to pathological conditions by sensing stimulation of exposed dentin. The functional properties and localization patterns of transient receptor potential (TRP) melastatin subfamily member 8 (TRPM8) and ankyrin subfamily member 1 (TRPA1) channels in odontoblasts remain to be clarified. We investigated the localization and the pharmacological, biophysical, and mechano-sensitive properties of TRPM8 and TRPA1 channels in rat odontoblasts. Menthol and icilin increased the intracellular free Ca(2+) concentration ([Ca(2+)]i). Icilin-, WS3-, or WS12-induced [Ca(2+)]i increases were inhibited by capsazepine or 5-benzyloxytriptamine. The increase in [Ca(2+)]i elicited by allyl isothiocyanate (AITC) was inhibited by HC030031. WS12 and AITC exerted a desensitizing effect on [Ca(2+)]i increase. Low-temperature stimuli elicited [Ca(2+)]i increases that are sensitive to both 5-benzyloxytriptamine and HC030031. Hypotonic stimulation-induced membrane stretch increased [Ca(2+)]i; HC030031 but not 5-benzyloxytriptamine inhibited the effect. The results suggest that TRPM8 channels in rat odontoblasts play a role in detecting low-temperature stimulation of the dentin surface and that TRPA1 channels are involved in sensing membrane stretching and low-temperature stimulation. The results also indicate that odontoblasts act as mechanical and thermal receptor cells, detecting the stimulation of exposed dentin to drive multiple cellular functions, such as sensory transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Dentin / drug effects
  • Dentin / metabolism
  • Male
  • Menthol / pharmacology
  • Odontoblasts / drug effects
  • Odontoblasts / metabolism*
  • Pyrimidinones / pharmacology
  • Rats
  • Rats, Wistar
  • TRPA1 Cation Channel
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*


  • Pyrimidinones
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPM Cation Channels
  • Trpa1 protein, rat
  • Trpm8 protein, rat
  • Menthol
  • icilin
  • Calcium

Grant support

This research was supported by an Oral Health Science Center Grant hrc8 from Tokyo Dental College, a Project for Private Universities matching fund subsidy from Ministry of Education, Culture, Sports, Science and Technology in Japan (2011–2013), and a Grant-in-Aid (No. 23592751/23792132) for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology in Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.