title: Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity.
abstract: Thermosensitive Transient Receptor Potential (TRP) channels are believed to respond to either cold or heat. In the case of TRP subtype A1 (TRPA1), there seems to be a species-dependent divergence in temperature sensation as non-mammalian TRPA1 is heat-sensitive whereas mammalian TRPA1 is sensitive to cold. It has been speculated but never experimentally proven that TRPA1 and other temperature-sensitive ion channels have the inherent capability of responding to both cold and heat. Here we show that redox modification and ligands affect human TRPA1 (hTRPA1) cold and heat sensing properties in lipid bilayer and whole-cell patch-clamp recordings as well as heat-evoked TRPA1-dependent calcitonin gene-related peptide (CGRP) release from mouse trachea. Studies of purified hTRPA1 intrinsic tryptophan fluorescence, in the absence of lipid bilayer, consolidate hTRPA1 as an intrinsic bidirectional thermosensor that is modified by the redox state and ligands. Thus, the heat sensing property of TRPA1 is conserved in mammalians, in which TRPA1 may contribute to sensing warmth and uncomfortable heat in addition to noxious cold.
authors.affiliation: Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, SE-221 00 Lund, Sweden.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Moparthi
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Universitätsstrasse 17, 91054 Erlangen, Germany.
authors.forename: Tatjana I
authors.initials: TI
authors.lastname: Kichko
authors.affiliation: Department of Anesthesiology and Intensive Care, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Eberhardt
authors.affiliation: Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, SE-221 85 Lund, Sweden.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Högestätt
authors.affiliation: Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, SE-221 00 Lund, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Kjellbom
authors.affiliation: Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, SE-221 00 Lund, Sweden.
authors.forename: Urban
authors.initials: U
authors.lastname: Johanson
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Universitätsstrasse 17, 91054 Erlangen, Germany.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reeh
authors.affiliation: Department of Anesthesiology and Intensive Care, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leffler
authors.affiliation: Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nuremberg, Egerlandstrasse 1, 91058 Erlangen, Germany.|IBGC, UMR 5095, Universite de Bordeaux, 1, rue Camille Saint Saëns, CS 61390, 33077 Bordeaux cedex, France.
authors.forename: Milos R
authors.initials: MR
authors.lastname: Filipovic
authors.affiliation: Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, SE-221 85 Lund, Sweden.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Zygmunt
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D000074025:TRPA1 Cation Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing / Q000502:physiology*; D014132:Trachea / Q000737:chemistry / Q000378:metabolism
chemical_list: D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; C475685:Trpa1 protein, mouse; D015740:Calcitonin Gene-Related Peptide