Fig. 3

Structural modifications of the resin acid derivatives affects channel activation. A, Molecular structures of dehydroabietic acid (DHAA, including numbering of some carbon atoms) and investigated resin acid derivatives with a carboxyl group. B, G(V) shifts (ΔV50) (hKV7.2/7.3 expressed in Xenopus oocytes) at pH 9 by 30 µM of indicated compound. Data = mean ± SEM. Color coding according to halogenation as indicated. G(V) shifts: DHAA: −5.3 ± 1.1 mV (n = 5); Wu13: −11.6 ± 0.6 mV (n = 6); Wu24: −17.6 ± 0.9 mV (n = 4); Wu60: −19.3 ± 1.4 mV (n = 6); Wu32: −13.6 ± 1.5 mV (n = 4); Wu36: −4.3 ± 0.5 mV (n = 5); Wu14: −22.9 ± 1.1 mV (n = 4); Wu27: −20.9 ± 2.0 mV (n = 5); Wu50: −13.3 ± 0.8 mV (n = 4). One-way ANOVA was used with Sidak's multiple comparison test. For comparison with DHAA (dotted line), the significance is given above each bar. ns, p > .05; *, p < .05; **, p < .01; ***, p < .001; ****, p < .0001. C, Molecular structures of investigated resin acid derivatives with a sulfonyl group. D, Concentration-response for ΔV50 (hKV7.2/7.3 expressed in Xenopus oocytes) at pH 7.4 for Wu109 and Wu161 as indicated. Data = mean ± SEM. Equation 3 for Wu109: ΔVMAX = −38.8 ± 4.5 mV, EC50 = 51.1 ± 12.6 µM, (n = 3–4). Equation 3 for Wu161: ΔVMAX = −31.7 ± 3.0 mV, EC50 = 22.7 ± 5.8 µM, (n = 4–8). E, G(V) shifts (ΔV50) (hKV7.2/7.3 expressed in Xenopus oocytes) at pH 9.0 (30 µM DHAA, Wu24, and Wu14 [for data see B]) or at pH 7.4 (Wu109: −14.5 ± 0.7 mV (n = 6); Wu199: −22.6 ± 2.6 mV (n = 4); Wu200: −27.6 ± 1.4 mV (n = 4). Data = mean ± SEM. Color coded as in B. ANOVA with Sidak's multiple comparisons test was used. ns, p > .05; *, p < .05; **, p < .01; ***, p < .001. F, Concentration-response for ΔV50 (hKV7.2/7.3 expressed in Xenopus oocytes) at pH 7.4 for Wu109, Wu199, and Wu200 as indicated. Data = mean ± SEM. Equation 3 for Wu199: ΔVMAX = −31.9 ± 1.8 mV, EC50 = 12.3 ± 2.2 µM, (n = 3–8). Equation 3 for Wu200: ΔVMAX = −37.2 ± 1.2 mV, EC50 = 11.7 ± 1.3 µM, (n = 4–7). For Wu109, see D. (G) G(V) shifts (ΔV50) (hKV7.2/7.3 expressed in Xenopus oocytes) at pH 7.4 by 30 µM of indicated compound. Data = mean ± SEM. Resin acid derivatives are color coded as in B. Data for RTG from Figure 2C. Data for Wu161 from Figure 1E. Data for Wu109, Wu199, and Wu200 from E. Wu181: −34.1 ± 3.1 mV (n = 5). ANOVA with Dunnett's multiple comparison test was used for comparison with RTG (dashed line). ns, p > .05; **, p < .01; ***, p < .001; ****, p < .0001