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Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine


Yao, Jing et al. (2021), Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine, Dryad, Dataset,


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. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.


The data was mainly collected from patch-clamp recordings.

Usage Notes

This dataset contains ten excel sheets including all the data used to analyze the inhibitory effect of the clinical medication dyclonine on thermal TRPV3 channel. Each excel sheet corresponds to a figure, and each statistical result in the figure can be found in the excel sheet. Information on how the measurements were done can be found in the associated manuscript.