Irritating channels: the case of TRPA1

• Published in: The Journal of physiology Vol. 589; no. 7; pp. 1543 - 1549
• Main Authors: Nilius, Bernd, Prenen, Jean, Owsianik, Grzegorz
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Amino Acid Sequence; Animals; Ankyrin Repeat; Calcium - metabolism; Calcium Channels - chemistry; Calcium Channels - genetics; Calcium Channels - metabolism; Cysteine - chemistry; Humans; Ion Channel Gating - physiology; Mice; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Permeability; Protein Structure, Tertiary; Symposium Section Reviews: The Bernd Nilius Festschrift – TRP Channels: From Structure to Disease; Transient Receptor Potential Channels - chemistry; Transient Receptor Potential Channels - genetics; Transient Receptor Potential Channels - metabolism; TRPA1 Cation Channel
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2010.200717

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.