Figure 8. Rundown of F508del-CFTR is partially rectified by P-ATP.

(A) Macroscopic recordings of F508del-CFTR or F508del/D1370N currents in response to the washout of 2 mM ATP (top and bottom) or 50 μM P-ATP (middle) for different durations. F508del-CFTR lost 78 ± 15 % (n = 4) of the initial currents after 180 seconds of ATP washout, similar to F508del/D1370N-CFTR, but 58 ± 8 % (n = 6) reduction was seen when the ligand was P-ATP (ATP vs P-ATP: p = 0.024). Of note, PKA can not use P-ATP for phosphorylation of CFTR. (Mihályi et al., 2020) (B) The relationship between τ₂ measuring the recovery from reversible rundown and the duration of ATP (or P-ATP) removal. The τ₂ after 180 seconds of washout was not included as the residual currents were too small for a reliable double-exponential fit. Each data point is compared to the F508del + ATP group at the same washout time. *p = 0.032 (P-ATP, 30 s), 0.007 (P-ATP, 60 s), and 0.003 (F508del/D1370N, 60 s) respectively. (C) A bar graph summarizing the fraction of reversible and irreversible rundown for F508del-CFTR opened by ATP (black), P-ATP (red), or F508del/D1370N-CFTR opened by ATP (blue). The proportion of irreversible rundown was reduced by P-ATP, but the percentage of reversible rundown remained similar. Each bar is compared to F508del-CFTR opened by ATP (black). #p (irreversible) = 0.042 (P-ATP, 10 s) and 0.041 (P-ATP, 60 s). n = 4 – 5 for F508del. n = 4 – 6 for F508del/D1370N.