Summary of initial in vitro data on effects of ivacaftor (VX-770) on human bronchial epithelial cells (HBEs) expressing the Gly551Asp CFTR mutation. a Potentiation of CFTR-mediated chloride (Cl−) secretion following treatment with ivacaftor. Chamber techniques were used to record the transepithelial current (I
T) resulting from CFTR-mediated Cl− secretion. To isolate the CFTR-mediated I
T, a basolateral-to-apical Cl− gradient was established, 30 μM amiloride was added to block the epithelial sodium channel (ENaC), and 10 μM (maximal effective concentration; EC99) forskolin (FSK) was applied to activate the CFTR. The concentration–response curve for ivacaftor in the presence of FSK is shown for Gly551Asp/Phe508del HBEs isolated from the bronchi of a single individual (filled circles; n = 16) and Phe508del HBEs isolated from the bronchi of the three individuals who responded to ivacaftor (open circles; n = 7–24). Left y-axis shows I
T responses; right y-axis shows I
T normalized to the 10 μM FSK-stimulated I
T in non-cystic fibrosis (CF) HBEs (mean ± standard error of the mean). Note that the error bars for the Phe508del HBEs were smaller than the symbol. b Increased airway surface liquid (ASL) following treatment with ivacaftor. Mean (n = 3–9) ASL volume in the absence (open bars) or presence (filled bars) of 10 μM ivacaftor and in the presence of 30 nM vasoactive intestinal peptide (VIP) and/or 20 μM CFTR inhibitor-172 (inh-172). c Increased ciliary beat frequency (CBF) following treatment with ivacaftor. Mean (± standard error of the mean; n = 6) CBF for wild-type HBEs (filled bars) or Gly551Asp/Phe508del HBEs (open bars) after a 5-day treatment with DMSO, 30 nM VIP, 10 μM ivacaftor, or 30 nM VIP with 10 μM ivacaftor. Single asterisk indicates significantly different (P < 0.05) from vehicle control in Gly551Asp/Phe508del HBEs; double asterisk indicates significantly different (P < 0.05) from vehicle control and ivacaftor alone. EC
half-maximum effective concentration. Reproduced with permission from Van Goor et al.