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 ED(50) for ACh-induced contractions (by 0.24 (SEM 0.07) mu mol litre(-1)). TEA 1 mmol litre(-1) but not glibenclamide 10 mu mol litre(-1) significantly augmented this increase in ED(50) (by an additional 0.17 (0.06) mu mol litre(-1)). In strips precontracted with ACh, TEA, but not glibenclamide, potentiated concentration-dependent relaxation induced by halothane. Incubation with YM934 0.32 mu mol litre(-1) increased significantly the ED(50) for ACh-induced contractions (from (0.02) to 0.55 (0.11) mu mol 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 mu mol litre(-1), YM934 concentration-dependent relaxation; 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.