Effect of Gln-1291 mutations on AMP-NH2 inhibition of CFTR Cl− current.
A and B, time courses showing the effect of AMP-NH2 added at 75 μm ATP on wild-type (Q1291) (A) versus Q1291F (B) CFTR Cl− current. Recordings (100 ms averages) are from excised inside-out membrane patches containing multiple wild-type (A) or Q1291F (B) CFTR channels. ATP and AMP-NH2 were present during the times and at the concentrations indicated by bars. ATP was added together with PKA catalytic subunit as described under “Experimental Procedures.” Holding voltage was −50 mV. C, quantitative data. Experiments were performed as shown in A and B with [ATP] = 75 μm. The percentage of current decrease with 5 mm AMP-NH2 was calculated as described in the legend to Fig. 3B for Ap5A. Columns show the means ± S.E. (error bars) of 15 (wild type), 11 (Q1291F mutant), and 5 (Q1291G mutant) individual experiments obtained from two (wild type) and three (Q1291F and Q1291G mutants) membrane patches. *, p < 0.001 compared with wild-type (Kruskal-Wallis one-way ANOVA on ranks followed by Dunn's method of all pairwise multiple comparisons).