TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP

Pflugers Arch. 2009 Oct;458(6):1093-102. doi: 10.1007/s00424-009-0703-x. Epub 2009 Aug 8.


Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would then activate termini of neighboring dorsal root ganglion (DRG) neurons. Here we show that adenosine triphosphate (ATP) is such a candidate molecule released from keratinocytes upon heating in the co-culture systems. Using TRPV1-deficient DRG neurons, we found that increase in cytosolic Ca(2+)-concentration in DRG neurons upon heating was observed only when neurons were co-cultured with keratinocytes, and this increase was blocked by P2 purinoreceptor antagonists, PPADS and suramin. In a co-culture of keratinocytes with HEK293 cells (transfected with P2X(2) cDNA to serve as a bio-sensor), we observed that heat-activated keratinocytes secretes ATP, and that ATP release is compromised in keratinocytes from TRPV3-deficient mice. This study provides evidence that ATP is a messenger molecule for mainly TRPV3-mediated thermotransduction in skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / physiology*
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Ganglia, Spinal / cytology
  • Glutamic Acid / metabolism
  • Hot Temperature
  • Humans
  • Keratinocytes / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Patch-Clamp Techniques
  • Sensory Receptor Cells / metabolism*
  • Serotonin / metabolism
  • Signal Transduction / physiology
  • Skin / metabolism
  • TRPV Cation Channels / physiology*


  • TRPV Cation Channels
  • Trpv3 protein, mouse
  • Serotonin
  • Glutamic Acid
  • Adenosine Triphosphate
  • Calcium