Astringency is a multimodal sensory experience resulting from complex interactions between chemical compounds and the oral environment, involving tactile, chemosensory and thermosensory pathways. Recent human studies have examined the role of the polymodal transient receptor potential (TRP) channels TRPV1 and TRPA1 in astringency perception; however, other thermo- and mechanosensitive TRP channels expressed in oral epithelial cells and in trigeminal neurons innervating the mouth and tongue may also contribute to this complex sensation. This study explored the effects of structurally distinct representatives of astringent compounds on TRPV2 and TRPC5 channels. Using patch-clamp electrophysiology, microfluorimetry, molecular modeling, and mutagenesis, we show that the auto-oxidation products of the most abundant green tea polyphenol (-)-epigallocatechin-3-gallate (oxi-EGCG) significantly increase the activation of rat TRPV2 while blocking the human orthologue. The plant-derived isoflavone genistein, but not its glycoside form genistin, potentiated human TRPV2 and sensitized TRPC5-mediated currents activated by depolarizing voltage and the alpha subunit of G-proteins. Tannic acid, another astringent substance, potentiated rat TRPV2 and inhibited human TRPV2 and TRPC5. Furthermore, we show that both channels can interact with mucin 1, a transmembrane glycoprotein present in the native oral environment. Our data also provide the first evidence of heat-induced activation of human TRPV2. Considering previous evidence for TRPV2 and TRPC5 expression in the oral cavity and their roles in oral pain and cancer, our findings indicate that these polymodal channels may participate not only in detecting specific astringent compounds, but also in mediating their broader health-related and anesthetic actions.

Faculty of Mathematics and Physics Institute of Physics Charles University Prague Czech Republic

Institute of Physiology Czech Academy of Sciences Prague Czech Republic

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