Effect of S6 aromatic residue mutations on IhERG by Cavalli-2. Representative current traces from Y652A (B) before and after application of 300 nm Cavalli-2 (Cav-2) and its WT control (A) are shown. C, mean ± S.E. fractional block data for Y652A IhERG tails following voltage commands to −20, 0, +20, and +40 mV. Data are from six cells. D, concentration-response relationships for inhibition of Y652A and WT IhERG tails at −40 mV by Cavalli-2 (n ≥ 5 for each concentration of each curve). E, representative current traces from F656A at −120 mV in high K+ before and after application of 1 μm Cavalli-2. F, concentration-response relationships for inhibition of F656A and WT IhERG tails at −120 mV in high K+. n ≥ 5 for each concentration of each curve. Error bars represent means ± S.E.