Selective inhibition of overactive warmth-sensitive Ca²⁺-permeable TRPV3 channels by antispasmodic agent flopropione for alleviation of skin inflammation.

ABSTRACT: The temperature-sensitive Ca²⁺-permeable TRPV3 ion channel is robustly expressed in the skin keratinocytes, and its gain-of-function mutations are involved in the pathology of skin lesions. Here, we report the identification of an antispasmodic agent flopropione that alleviates skin inflammation by selective inhibition of TRPV3. In whole-cell patch clamp recordings, flopropione selectively inhibits macroscopic TRPV3 currents in a concentration-dependent manner with an IC₅₀ value of 17.8 ± 3.5 μM. At the single-channel level, flopropione inhibits TRPV3 channel open probability without alteration of its unitary conductance. In an in vivo mouse model of skin inflammation induced by the skin sensitizer DNFB, flopropione also alleviates dorsal skin lesions and ear skin swe

SUBMITTER: Xu Y 

PROVIDER: S-EPMC10828444 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature