Additive effects of NO₃⁻ and VX-770 on WT-CFTR gating. (A) NO₃⁻ further increases macroscopic WT-CFTR current in the presence of VX-770. Replacing bath Cl⁻ with NO₃⁻ enhances the PKA-phosphorylated WT-CFTR current in the presence of VX-770. (B) A comparison of residual currents in the same patch after removal of ATP in different conditions as indicated. These “ATP-independent” activities are negligibly small in Cl⁻ bath before the application of VX-770. On the other hand, more prominent channel currents are seen in NO₃⁻ bath. A similar increase of this ATP-independent activity by VX-770 was reported previously (Jih and Hwang, 2013; Lin et al., 2014). It is noted that a much higher current of VX-770–treated CFTR remains after ATP washout in NO₃⁻ bath. (C) Single-channel behavior of VX-770–potentiated WT-CFTR in Cl⁻ or NO₃⁻ bath. Comparing these two 40-s traces, we noted longer open events and shorter closed events in NO₃⁻. (D) Summary of the additive effect of NO₃⁻ and VX-770 on single-channel kinetics of WT-CFTR. P_o, τ_o, and closed time τ_c are as follows: 0.70 ± 0.02, 720 ± 85 ms, and 299 ± 10 ms for Cl⁻; and 0.83 ± 0.02, 1,394 ± 283 ms, and 254 ± 20 ms for NO₃⁻ (n = 5). The error bars represent the SEM of the mean.