Direct activation of the ion channel TRPA1 by Ca2+.
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.
Zurborg
Sandra
S
Klinik für Anaesthesiologie und operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Yurgionas
Brian
B
Jira
Julia A
JA
Caspani
Ombretta
O
Heppenstall
Paul A
PA
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D003080:Cold Temperature; D003952:Diagnostic Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D020832:EF Hand Motifs / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D000074025:TRPA1 Cation Channel; D014162:Transfection / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
D018712:Analgesics, Non-Narcotic; D015220:Calcium Channels; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D002217:Carbachol; D002118:Calcium