The S. flavescens alkaloid aloperine activates KCNQ5. All error bars indicate SEM. (A) Image of dried S. flavescens root slices used in this study. (B) Chemical structures of aloperine, matrine, and oxymatrine plotted using Jmol. (C) Mean TEVC current traces showing effects of aloperine, matrine, and oxymatrine (all 100 µM) individually on KCNQ5 expressed in Xenopus oocytes (n = 4 to 6). (D) Mean tail current versus prepulse voltage relationships for the traces as in C (n = 4 to 6). (E) Mean normalized tail currents (G/Gmax) versus prepulse voltage relationships for the traces as in C (n = 4 to 6). (F) Effects of aloperine, matrine, and oxymatrine (100 µM) individually on resting membrane potential (EM) of unclamped oocytes expressing KCNQ5 (n = 4 to 6). n.s., not statistically significant (P > 0.05). (G) Voltage dependence of effects of aloperine, matrine, and oxymatrine (100 µM) individually on KCNQ5 (from traces as in C; n = 4 to 6). (H) Mean effects of aloperine, matrine, and oxymatrine (100 µM) individually on KCNQ5 V0.5activation (from traces as in C; n = 4 to 6). (I) Mean effects of aloperine, matrine, and oxymatrine (each 1 µM) combined (“Cocktail”) on KCNQ5 expressed in Xenopus oocytes (n = 5). (Upper) Mean TEVC traces; (Lower Left) mean tail current versus prepulse voltage relationships; (Lower Right) mean normalized tail currents (G/Gmax) versus prepulse voltage relationships. (J) Comparison of effects of aloperine (100 µM), cocktail, and S. flavescens extract (1%) on KCNQ5 activity, quantified as current fold change versus voltage (n = 5 to 6).