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. 2019 Jun 17;8:e46450. doi: 10.7554/eLife.46450

Figure 2. CFTR current stimulation by Vx-770 is fully reversible.

Figure 2.

(a) Macroscopic WT CFTR channel current, elicited in an inside-out patch by exposure to 2 mM ATP (gray bar), is enhanced ~4-fold by application of a 1x saturated (~62 nM) Vx-770 solution (red bar), and relaxes back to its pre-drug level following drug removal. Red line is a fitted exponential with time constant (τ) indicated. Channels had been pre-phosphorylated by an ~1-min exposure to 300 nM PKA catalytic subunit, membrane potential is -40 mV. (b) 1-min segments of recording from a single pre-phosphorylated WT CFTR channel gating in 2 mM ATP before drug exposure (top), in the presence of 0.05x saturated (~3 nM) Vx-770 (center; segment starts ~4 min after drug addition), and long after Vx-770 removal (bottom, segment starts ~9 min after drug removal). (c) Open probabilities (left), opening rates (center), and closing rates (right) of single pre-phosphorylated WT CFTR channels gating in 2 mM ATP, before (dark gray bars), during (red bars), and after (light gray bars) exposure to 0.05x saturated (~3 nM) Vx-770. Bars show mean ± S.E.M. from 9 experiments.