Specificity of CFTR inhibition by CFTRinh-172. (a) Alternative Cl– channels. Left: UTP (100 μM) stimulated Ca2+-dependent Cl– secretion measured in short-circuit current measurements on airway epithelial cells in the absence and presence of 5 μM CFTRinh-172. Right: Volume-activated Cl– current (hypotonic 250 mosM/kg H2O) measured in whole-cell patch-clamp experiments on FRT cells. Currents were recorded in the absence and presence of 5 μM CFTRinh-172. (b) MDR-1 activity. 3H-vincristine accumulation in 9HTEo-/Dx cells with upregulated MDR-1 expression. Intracellular vincristine was measured with and without verapamil (100 μM) or CFTRinh-172 (5 μM) (SE; n = 3). (c) ATP-sensitive K+ channels. Left: Representative membrane potential recording from a pancreatic β cell (INS-1) perfused extracellularly with CFTRinh-172, diazoxide (100 μM), and glibenclamide (glib; 10 μM). Right: Averaged changes in membrane potential (ΔmV) caused by indicated maneuvers (SE; n = 4). PD, potential difference.