Mechanisms of Proton Inhibition and Sensitization of the Cation Channel TRPV3

The study explored how protons regulate the TRPV3 cation channel, which is crucial for hair morphogenesis and skin barrier function. Researchers found that extracellular protons inhibit TRPV3 activation through the aspartate residue D641, while intracellular protons sensitize the channel via C-terminal residues E682, E689, and D727. Mutations in these residues enhanced the channel's sensitivity to agonists and shifted it from a naive to a sensitized state. These findings provided insights into TRPV3's role in skin disorders and its regulation under acidic conditions, highlighting the complex interactions between protonation sites and channel function.