Additive effect of VX-770 and ATP in regulation of phosphorylated WT CFTR.
A, representative iodide efflux traces mediated by proteoliposomes containing pre-phosphorylated WT-CFTR in the absence or presence of 1 mm Mg-ATP and the absence or presence of 10 μm VX-770 as indicated, also see summary bar graphs in Fig. 6C. Data in gray indicate the sum of the efflux rates +VX-770 and +ATP traces. B, representative iodide efflux traces mediated by proteoliposomes containing pre-phosphorylated WT-CFTR in the absence (gray) or presence (black) of 2 μm VX-770 and in the presence of 0.1 or 2 mm ATP. C, no effect of VX-770 on ATP dependence of WT-CFTR flux activity in the presence or absence of VX-770 (2 μm). Data points represent initial rates mediated by PKA-phosphorylated WT-CFTR proteoliposomes pretreated in the presence of 2 μm VX-770 (+VX-770; closed circles) or in its absence but in the presence of DMSO vehicle (−VX-770; open circles) at a range of Mg-ATP concentrations. Although treatment with VX-770 significantly increased flux activity (p < 0.0001), to 1.4-fold the value in its absence, data were normalized to 1 in the absence of ATP in both cases to illustrate similarity of the ATP dependence. Data represent the mean of three traces ± S.E.