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 myocytes reveal that 1-benzyl-7-chloro-4-(n-pentylimino)-1,4-dihydroquinoline hydrochloride (WIN 17317-3), a potent blocker of Kv1.3 channels and potential immunomodulator, reduces, in a reversible manner and at low micromolar concentrations, K+ currents through Ca2+-activated high conductance K+ channels (BK channels). Blockade of BK channels is thought to account for the stimulatory effect of WIN 17317-3 on the contractility of guinea-pig bladder. This effect is not modified by tetrodotoxin (1 microM), but is abolished by nifedipine (0.1 microM). In conclusion. WIN 17317-3 lacks selectivity for the Kv1.3 channels, its postulated target for immunosuppression.
Vianna-Jorge
R
R
Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil.
Oliveira
C F
CF
Ponte
C G
CG
Suarez-Kurtz
G
G
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002469:Cell Separation; D002478:Cells, Cultured; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D051664:Kv1.3 Potassium Channel; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011804:Quinolines / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects
D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011804:Quinolines; C094805:WIN 17317-3