Fig. 5.
Macroscopic kinetics and magnitude of the potentiator-stimulated CFTRV232D currents. Macroscopic Cl− currents from excised macropatches were measured. A: representative current trace recorded at −40 mV. After baseline current measurement (0–40 s), VRT-532 (10 μM) perfusion resulted in a rapid increase of the inward current, which stabilized over 60 s and then returned to baseline following potentiator washout. Gray curves depict single-exponential fits to the time course of current stimulation [mean time constant (τon)=6.2 ± 0.9 s, n=8] and recovery after VRT-532 washout from the patch (τoff=24.0 ± 2.2 s, n=5). In contrast, Corr-4a (2 μM) was not found to stimulate current. B: summary of fold stimulation of current (Ifold-stim) achieved with CFTR modulators. Ifold-stim was increased 3.3 ± 1.0-fold with VRT-532 [10 μM, n=9 (**P < 0.050)] but was insensitive to Corr-4a [2 μM, n=6 (P=0.143)]. Currents were recorded using HEK-293 cells, as described in Fig. 4 legend.