Figure 11.
DHAA derivatives open the human M channel. (A) Currents before and after application of 100 µM Wu161. Steps to voltages between ‒120 and 20 mV (in 5-mV increments) started at t = 0.7 s. At t = 2.7 s, the voltage was switched to ‒10 mV. Traces at voltage = ‒20 mV in red. (B) G(V) curves for the cell in A. G(V) shift = ‒23.8 mV. (C) G(V) shifts for compounds with different stalk lengths (100 µM). Mean ± SEM (n = 3–6). DHAA(p1) at pH = 10. Permanently charged Wu164(p2), Wu161(p3), and Wu154(p5) at pH = 7.4. (D) Compounds with different valences (100 µM). pH = 7.4. Mean ± SEM (n = 3–5). ***, P < 0.001, significantly different from 0. (E) Concentration–response curves. Mean ± SEM (n = 3–4). Eq. 3: c½ = 62 µM, ΔVMax = ‒35.0 mV (Wu161); c½ = 12 µM, ΔVMax = ‒42.1 mV (Wu181).