Structural mechanism of TRPV3 channel inhibition by the anesthetic dyclonine

Skin diseases occur in all cultures, at all ages and affect up to 70% of population. TRPV3 channel in the membrane of skin cells keeps them healthy and protects against wounds but is also associated with skin diseases when hyperactive. Sought after drugs targeting hyperactive TRPV3 are largely missing. The FDA-approved anesthetic dyclonine has recently been found to block TRPV3 activity but the molecular mechanism of this block remained a mystery. We have uncovered the mechanism of block: dyclonine binds deep inside TRPV3 and ‘tightens’ up its pore against ion passage. This discovery helps to design new drugs for the treatment of devastating skin diseases.