Direct activation of the ion channel TRPA1 by Ca2+

Nat Neurosci. 2007 Mar;10(3):277-9. doi: 10.1038/nn1843. Epub 2007 Jan 28.

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 Ca(2+) activates human TRPA1 via an EF-hand domain and that cold sensitivity occurs indirectly (and nonphysiologically) through increased [Ca(2+)](i) during cooling in heterologous systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / physiology*
  • Carbachol / pharmacology
  • Cell Line
  • Cold Temperature
  • Diagnostic Imaging / methods
  • Dose-Response Relationship, Drug
  • EF Hand Motifs / physiology
  • Humans
  • Intracellular Fluid / metabolism
  • Luminescent Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mutagenesis / physiology
  • Nerve Tissue Proteins / physiology*
  • Patch-Clamp Techniques / methods
  • TRPA1 Cation Channel
  • Transfection / methods
  • Transient Receptor Potential Channels / drug effects
  • Transient Receptor Potential Channels / physiology
  • Transient Receptor Potential Channels / radiation effects

Substances

  • Analgesics, Non-Narcotic
  • Calcium Channels
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • Carbachol
  • Calcium