Fig. 2.

Patch-clamp analysis of mechanism of CFTR block by multidrug resistance-associated protein inhibitors. (A–C) Representative whole-cell recordings of CFTR Cl⁻ currents. CFTR was activated with forskolin (0.5 μM). Each panel shows superimposed membrane currents elicited at different membrane potentials (in 20 mV steps) in the absence (left) and in the presence (right) of sulfinpyrazone, probenecid, or benzbromarone at the indicated concentrations. The range of applied membrane potentials was–80 to +80 mV for sulfinpyrazone and probenecid and–100 to +60 mV for benzbromarone. (D) Voltage-dependence of CFTR currents in the absence and presence of inhibitors. Membrane currents are normalized for the value measured at–80 mV in the absence of inhibitors. (E) Cell-attached recording of a single CFTR channel. Traces show a single burst of channel opening in absence and presence of probenecid (400 μM). Openings are represented by downward deflections from the baseline.