WIN 17317-3 blocks Ca2+-activated K+ channels and enhances motility of guinea-pig detrusor muscle

Patch-clamp experiments in both clonal GH3 cells and guinea-pig bladder myo cytes reveal that 1-benzyl-7-chloro-4-(n-pentylimino)-1,4-dihydroquinoline hydrochloride (WIN 17317-3). a potent blocker of Kv1.3 channels and potenti al immunomodulator, reduces, in a reversible manner and at low micromolar c oncentrations, K+ currents through Ca2+-activated high conductance K+ chann els (BK channels). Blockade of BK channels is thought to account for the st imulatory effect of WIN 17317-3 on the contractility of guinea-pig bladder. This effect is not modified by tetrodotoxin (1 muM), but is abolished by n ifedipine (0.1 muM). In conclusion, WIN 17317-3 lacks selectivity for the K v1.3 channels, its postulated target for immunosuppression. (C) 2001 Elsevi er Science B.V. All rights reserved.