Figure 6. Effect of disopyramide, D-sotalol and flecainide on WT and T618I I_hERG under conventional voltage clamp.

(A) Upper traces show I_hERG elicited by voltage protocol shown in the lower panel in control solution and after exposure to 10 µM disopyramide (Diso). Ai shows data for WT I_hERG, whilst Aii shows data for T618I I_hERG. Note different current scales in Ai and Aii. (B) Concentration response relations for inhibition of WT and T618I I_hERG by disopyramide. Fractional inhibition of I_hERG was assessed for I_hERG tails at each of 3 concentrations for WT I_hERG (n = 5 cells at 1 µM; 13 at 10 µM and 5 at 100 µM; incorporating data from [26], with additional data from a further 8 experiments for 10 µM disopyramide) and 4 for T618I I_hERG (n = 4 to 5 cells per concentration). (C) Concentration response relations for inhibition of WT and T618I I_hERG by D-sotalol. Fractional inhibition of I_hERG was assessed for I_hERG tails at each of 3 sotalol concentrations for WT I_hERG (n = 5 to 9 cells at each concentration) and 4 for T618I I_hERG (n = 5 to 6 cells per concentration). (D) Concentration response relations for inhibition of WT and T618I I_hERG by flecainide. Fractional inhibition of I_hERG was assessed for I_hERG tails at each of 4 flecainide concentrations for WT I_hERG (n = 5 to 12 cells per concentration) and T618I I_hERG (n = 5 to 6 cells per concentration).