Halothane and potassium channels in airway smooth muscle

Earlier studies have suggested that halothane may relax smooth muscle in part by opening adenosine triphosphate-sensitive potassium (K(ATP)) channels. We tested this hypothesis in vitro by examining the interaction of halothane with glibenclamide, a K(ATP) channel blocker, and YM934, a K(ATP) channel opener, in strips of canine tracheal smooth muscles mounted in an organ bath system. To examine the specificity of any effects of halothane on the K(ATP) channel, we assessed the interaction of halothane with tetraethylammonium (TEA), an antagonist of the large-conductance, calcium-activated potassium channel. Experiments were conducted with drugs added before exposure to increasing concentrations of acetylcholine (ACh), and with drugs added after stable increases in force produced by ACh were achieved (ACh precontraction). Exposure to halothane 0.62 mmol litre^-1 (equivalent to approximately 2 MAC) increased significantly the ED₅₀ for ACh-induced contractions (by 0.24 (SEM 0.07) μmol litre^-1). TEA 1 mmol litre^-1 but not glibenclamide 10 μmol litre^-1 significantly augmented this increase in ED₅₀ (by an additional 0.17 (0.06) μmol litre^-1). In strips precontracted with ACh, TEA, but not glibenclamide, potentiated concentration-dependent relaxation induced by halothane. Incubation with YM934 0.32 μmol litre^-1 increased significantly the ED₅₀ for ACh-induced contractions (from 0.12 (0.02) to 0.55 (0.11) μmol litre^-1), an increase not affected by exposure to halothane 0.72 mmol litre^-1. When added to strips precontracted with approximately ACh 0.3 μmol litre^-1, YM934 produced concentration-dependent relaxation; halothane had little effect on this relaxation. These results do not support the hypothesis that halothane relaxes canine tracheal smooth muscle in part by opening K(ATP) channels.