Fig. 5

Effect of TS3 on CFTRΔF508 mediated cAMP-activated chloride current. (A) Polarized monolayers of FRT cells expressing CFTRΔF508 were incubated for 48 hr with TS3 (1 or 5 µM, as indicated) or the equivalent amount of DMSO. The monolayers were subsequently incubated in TS3-free growth medium for the time (hr) indicated, mounted in Ussing chambers, and transepithelial chloride currents were measured after activation with 10 µM forskolin and 100 µM IBMX. Results represent the mean ±SEM for the number of experiments (n) indicated. Five µM TS3 treatment resulted in a significant difference from the respective control (p < 0.01, two-tailed t-test) for wash out time points 0 hr (n = 4), 9 hr (n = 15), and 18 hr (n = 3). One µM TS3 treatment resulted in a significant difference from the respective control (p < 0.01, two-tailed t-test) for wash out time point 0 hr (n = 4). For all other time points n = 4 (or greater). (B) Representative tracing for control and 5 µM TS3-treated cells after 9 hr of incubation in TS3-free growth medium. The bars indicate the presence of cAMP agonists (10 µM forskolin and 100 µM IBMX) and CFTR inhibitor (2 mM DPC). The dashed line represents the baseline current, before activation with cAMP agonists.