Competition between NPPB, 3NB, and 3PP for affecting hydrolytic closing rate. (A–C) Macroscopic WT CFTR currents at −80 mV, elicited by brief applications of 2 mM ATP (gray bars) in the absence of drug, or in the presence of either 210 µM NPPB (A, brown bar) or the following drug combinations: (A) 20 mM 3PP (red bar) plus 210 µM NPPB (brown bar), (B) 32 mM 3NB (blue bar) plus 210 µM NPPB (brown bar), and (C) 32 mM 3NB (blue bar) plus 20 mM 3PP (red bar). Current decay time courses after ATP removal were fitted by single exponentials (colored lines), and time constants are indicated. (D) Macroscopic closing rates, obtained as the inverses of fitted time constants (see Materials and methods), under control conditions (gray bar) or in the presence of 210 µM NPPB (brown bar), 32 mM 3NB (blue bar), or 20 mM 3PP (red bar), or their combinations (striped bars, same color coding). Horizontal lines illustrate the predicted closing rates in mixtures (see Materials and methods), assuming either completely independent (yellow lines) or mutually exclusive (green lines) binding of the coapplied drugs at their respective gating sites. Blue and red bars were replotted from Fig. 6 C. Mean ± SEM is shown.