![]() Natural plant products such as camphor ( Moqrich et al., 2005), carvacrol, eugenol, thymol ( Xu et al., 2006), and the pharmacological compound 2-aminoethoxydiphenyl borate (2-APB) ( Chung et al., 2004a Colton and Zhu, 2007) also activate TRPV3. TRPV3 is sensitive to innocuous temperatures above 30–33☌ and exhibits an increased response at noxious temperature ( Chung et al., 2005 Xu et al., 2002). TRPV3 integrates a wide spectrum of physical and chemical stimuli ( Luo and Hu, 2014). As a polymodal cellular sensor, transient receptor potential vanilloid-3 (TRPV3) channel is abundantly expressed in skin keratinocytes ( Chung et al., 2004b Peier et al., 2002 Xu et al., 2002) and in cells surrounding the hair follicles ( Cheng et al., 2010). Transient receptor potential (TRP) channels belong to a family of calcium-permeable and nonselective cation channels, essential for body sensory processing and local inflammatory development ( Clapham, 2003). The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive therapeutics for skin inflammation. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. ![]() ![]() Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted syndrome in humans. The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. ![]()
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