Fig. 1.
Charged capsaicin derivates stimulate TRPV1-dependent calcium influx but fail to induce electrical currents. (A) Three tetraakylammonium capsaicin derivatives bearing permanent positive charges are shown. (B) Representative traces of normalized Ca2+ signals induced by extracelluar application of capsaicin or derived analogs. Signals were normalized to the values from final application of a saturating dose of capsaicin. (C) Dose–response curves of evoked Ca2+ signals of three capsaicin analogs are overlaid for comparison with the parental compound capsaicin. (D) A total of 100 μM cap-ET applied directly to the cytoplamsic side of an inside-out patch from a HEK cell expressing rat TRPV1 induced a barely detectable electric current compared with full activation of TRPV1 by 30 μM capsaicin. The TRPV1 current sensitized by 10 μM PAO, an oxidative chemical that potentiates the receptor, exhibited a recordable but small current activated by 100 μM cap-ET.