Figure 4. Potential deleterious effect of VX‐770 at high concentrations observed for ΔI1234_R1239‐CFTR in a heterologous expression system.

• A, B
  Immunoblot (A) and quantitation (B) of ΔI1234_R1239‐CFTR expression following pharmacological correction (VX‐809) in the absence (DMSO) and presence of chronic (24 h) VX‐770 treatment (0.1, 1, and 10 μM; mean ± SEM, n = 3 biological replicates). Band B, black arrowhead; band C, white arrowhead. Statistical significance tested using two‐way ANOVA with Tukey's multiple comparisons test.
• C, D
  Representative traces (membrane depolarization assay) (C) and quantitation (D) of ΔI1234_R1239‐CFTR function following pharmacological correction (VX‐809) in the absence (DMSO) and presence of chronic (24 h) VX‐770 treatment (10 μM) and acute activation (VX‐770/forskolin; mean ± SEM, n = 8 biological replicates). Statistical significance tested using two‐way ANOVA with Tukey's multiple comparisons test.