Figure 5.

Effects of the Y652A and F656A mutations on the action of KB-R7943. (A) The traces in panels Ai and Aii show, respectively, WT I_hERG and Y652A I_hERG elicited in the absence and presence of 100 nM KB-R7943. The corresponding voltage protocol is shown in panel Aiii. (B) Mean data indicating effects of three concentrations of KB-R7943 on Y652A I_hERG, fitted by Equation 1 to give the IC₅₀ and n_H values given in the text. The concentration–response relation for WT I_hERG (identical to that shown in Figure 1) is shown overlain, for comparative purposes. (C) The traces in panels Ci and Cii show, respectively, WT I_hERG and F656A I_hERG elicited in the absence and presence of 1 µM KB-R7943. The corresponding voltage protocol is shown in panel Ciii and its inset. Experiments performed with high (94 mM) [K⁺]_e. (D) Mean data indicating effects of three concentrations of KB-R7943 on each of WT and F656A I_hERG tails, measured at −120 mV, fitted by Equation 1 to give the IC₅₀ and n_H values given in the text. For A and C, the horizontal dashed lines are drawn at the level of the current at the pre-pulse of −40 or −120 mV, against which peak tail current amplitudes were measured. For B and D, numbers in parentheses indicate numbers of replicates at each drug concentration tested on WT and mutant channels.