Skip to main content
. 2019 Jun 17;8:e46450. doi: 10.7554/eLife.46450

Figure 5. Model fitting of activation/deactivation time courses in response to cytosolic addition/removal of Vx-770.

(a-d) Cartoon representation of schemes with one (a, b) or two (c, d) drug binding sites, and one (a, c) or two (b, d) membrane compartments (cytoplasmic, bottom; extracellular, top). (e) Fit parameters obtained from global fits of Schemes 3 (left column) and 4 (right column) to the data set shown in f. *Parameters kin and kout were constrained through kin/kout = Doct/wat(pH=7.1) = 62580. Parameters Kd;mem, K0.5;mem, and K0.5;aq were calculated from the fit parameters as described in Materials and methods. (f) Pair of normalized macroscopic WT CFTR current activation/deactivation time courses recorded in response to cytosolic addition/removal of 0.01x saturated (gray trace) and 1x saturated (black trace) concentrations of Vx-770 (replotted from Figure 4a), and ensemble fits by the models in a–d (colored lines; green, Scheme 1, pink, Scheme 2, blue, Scheme 3, red, Scheme 4). See also Figure 5—figure supplement 1.

Figure 5.

Figure 5—figure supplement 1. Scheme 2 adequately fits individual on- and off- time courses but not the global data set.

Figure 5—figure supplement 1.

Pair of normalized macroscopic WT CFTR current activation/deactivation time courses recorded in response to cytosolic addition/removal of 0.01x saturated (gray trace) and 1x saturated (black trace) concentrations of Vx-770 (replotted from Fig. 5f), and fits by Scheme 2 (colored lines). Pink: fit of Scheme 2 to on- time course of the gray current trace (solid pink line), and off- time course predicted for the same trace by the obtained fit parameters (dashed pink line). Blue: fit of Scheme 2 to the entire gray current trace (solid blue line), and time course predicted for the black current trace using the same parameters (dashed blue line). Red: fit of Scheme 2 to the entire black current trace (solid red line), and time course predicted for the gray current trace using the same parameters (dashed red line). Green lines replot, as a comparison, the global fit of the entire data set by Scheme 1 (from Figure 5).