Figure 7.

Identification of non-downregulating potentiators with efficacy similar to VX-770. (A–C,left) Representative I_sc traces of polarized CFBE cells expressing the indicated CFTR2 mutants. The cells were incubated for 24 h with VX-809 (3 μM, red traces) with and without 10 μM P12 (blue), A04 (green) or H02 (yellow). I_sc of mutant CFTR was stimulated with forskolin (20 μM) and 10 μM of the respective long-term treatment potentiator. Non-potentiator pre-treated cells were stimulated with 3 μM VX-770. CFTR was inhibited with CFTR_inh-172 (20 μM). Measurements were performed in the presence of a basolateral-to-apical chloride gradient after basolateral permeabilization with amphotericin B (100 μM). (A–C, right) Quantification of maximal currents performed similarly as in Fig. 5 F. All experiments are n = 2, error bars are SEM.