A: Representative ISC tracing. Calu-3 cells initially studied in Ringers solution followed by 1) mucosal low- Cl− solution, 2) addition of 20 μM forskolin, 3) addition of 1mg/mL quinine, and 4)addition of 200 μM glybenclamide. B: After maximal activation of CFTR, addition of high-dose quinine (1 mg/ml) modestly increased apparent ISC in a chloride secretory gradient (17.0 ± 3.9 μA/cm2, *p<0.005 compared to forskolin alone, n=18, ±SEM) and was partially inhibited by glybenclamide (*p<0.005, n=18, ±SEM). The apparent reversal of ISC due to quinine in a reversed chloride gradient is attributable to increased paracellular permeability (*p<0.001, n=14, ±SEM).