Inhibition of locked-open CFTR by CFTRinh-172. CFTR channels were locked into an open state by using ATP plus PPi for WT-CFTR (A) or ATP for E1371S-CFTR (B). Once a steady-state current was attained, CFTRinh-172 was applied. In either case, the current was inhibited nearly completely. During the activation period, the short flat and vertical lines are a result of saturation of the amplifier and subsequent changes in the amplifier gain. (C) Dose–response relationships of CFTRinh-172 for WT-CFTR locked open by PPi (green symbols) and E1371S-CFTR locked open with ATP (blue symbols). Each data point represents values determined from four to nine patches. The fitted dose–response curve for WT channels gated with ATP was shown for comparison (red line). Although an accurate curve fit for the dose response cannot be obtained for PPi locked-open channels, a rough estimate of the IC50 of ∼10 nM seems reasonable.