title: Sensitization of TRPA1 by Protein Kinase A.
abstract: The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.|Institute of Physiology, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Jannis E
authors.initials: JE
authors.lastname: Meents
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.|Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany.|Center for Physiology and Pharmacology, Medical University Wien, Wien, Austria.
authors.forename: Michael J M
authors.initials: MJ
authors.lastname: Fischer
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.|Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
authors.forename: Peter A
authors.initials: PA
authors.lastname: McNaughton
mesh_terms: D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism* / Q000502:physiology; D000081007:Cymenes; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D039821:Monoterpenes / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D000074025:TRPA1 Cation Channel; D014162:Transfection; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D000081007:Cymenes; D039821:Monoterpenes; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D005576:Colforsin; C073316:carvacrol; D017868:Cyclic AMP-Dependent Protein Kinases