Figure 4.
Figure 4. Prolonging the mean open time of CFTR increases the potency of CFTRinh-172. (A) Representative single-channel trace for D1370N-CFTR, a hydrolysis-deficient mutant with a mean open time of ∼1 s. (B) A continuous current recording showing a reversible inhibition of macroscopic D1370N-CFTR currents by 1 µM CFTRinh-172. (C) Dose–response relationships of CFTRinh-172 for WT-CFTR gated by ATP or P-ATP and D1370N-CFTR gated by ATP. Note a graded leftward shift of the dose–response relationship as the mean open time is prolonged. The experimental data were fitted with the Hill equation. Fitting parameters: for P-ATP–gated WT channels: IC50 = 0.37 ± 0.22 µM and Hill coefficient, n = 0.69 ± 0.38; for D1370N-CFTR: IC50 = 0.064 ± 0.007 µM and n = 1.26 ± 0.17. Data points represent the average values determined from 4–14 patches.

Prolonging the mean open time of CFTR increases the potency of CFTRinh-172. (A) Representative single-channel trace for D1370N-CFTR, a hydrolysis-deficient mutant with a mean open time of ∼1 s. (B) A continuous current recording showing a reversible inhibition of macroscopic D1370N-CFTR currents by 1 µM CFTRinh-172. (C) Dose–response relationships of CFTRinh-172 for WT-CFTR gated by ATP or P-ATP and D1370N-CFTR gated by ATP. Note a graded leftward shift of the dose–response relationship as the mean open time is prolonged. The experimental data were fitted with the Hill equation. Fitting parameters: for P-ATP–gated WT channels: IC50 = 0.37 ± 0.22 µM and Hill coefficient, n = 0.69 ± 0.38; for D1370N-CFTR: IC50 = 0.064 ± 0.007 µM and n = 1.26 ± 0.17. Data points represent the average values determined from 4–14 patches.

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