title: Irritating channels: the case of TRPA1.
abstract: Transient receptor potential (TRP) channels have been extensively studied over the past years. Yet, in most cases, the gating mechanisms of these polymodal cation channels still remain a puzzle. Using the nociceptive channel TRPA1 as an example, we discuss the role of dynamic regulation of the pore size (pore dilatation) on channel gating. Additionally, we critically revise current knowledge of the role of intracellular domains, such as ankyrin repeats and EF hand motifs, in channel activation and function. Finally, we assess some problems inherent to activation of TRPA1 by the reaction of electrophilic compounds with the nucleophilic thiol sink of N-terminal reactive cysteines.
authors.affiliation: Department of Physiology, Campus Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. bernd.nilius@med.kuleuven.be
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Jean
authors.initials: J
authors.lastname: Prenen
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Owsianik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D017434:Protein Structure, Tertiary; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D003545:Cysteine; D002118:Calcium