pHi modulates CFTR Cl− current. A, time courses of wild-type CFTR Cl− current in excised inside-out membrane patches. In this and subsequent figures, unless otherwise indicated, ATP (0.3 mm) and PKA (75 nm) were continuously present in intracellular solutions, which were adjusted to the indicated pHi; voltage was −50 mV, and there was a large Cl− concentration gradient across the membrane ([Cl−]int, 147 mm; [Cl−]ext, 10 mm). For the purpose of illustration, time courses have been inverted, and upward deflections represent inward currents. B, effects of pHi on CFTR Cl− currents. Data are means ± S.E. (n = 6) expressed as a percentage of the control current at pHi 7.3. The asterisks indicate values that are significantly different from the control (p < 0.05). C, relationship between intracellular proton concentration ([Hi+]) and CFTR activity. Data from B are plotted versus [Hi+]. The continuous line is the fit of a hyperbolic function to the mean data (y = y0 + ax/(b + x), where y0 = 70.9, a = 84.7, and b = 8.8 × 10−8; r = 0.99). Error bars are smaller than symbol size except where shown.