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 (KATP) channels. We tested this hypothesis in vitro by examining the interaction of halothane with glibenclamide, a KATP channel blocker, and YM934, a KATP 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 KATP 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) mumol litre-1). TEA 1 mmol litre-1 but not glibenclamide 10 mumol litre-1 significantly augmented this increase in ED50 (by an additional 0.17 (0.06) mumol litre-1). In strips precontracted with ACh, TEA, but not glibenclamide, potentiated concentration-dependent relaxation induced by halothane. Incubation with YM934 0.32 mumol litre-1 increased significantly the ED50 for ACh-induced contractions (from 0.12 (0.02) to 0.55 (0.11) mumol 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 mumol 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 KATP channels.
Fukushima
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T
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
Hirasaki
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Jones
K A
KA
Warner
D O
DO
D000109:Acetylcholine / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines; D018678:Cholinergic Agents / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014132:Trachea
D018685:Anesthetics, Inhalation; D048588:Benzoxazines; D018678:Cholinergic Agents; D003497:Cyclic N-Oxides; D007004:Hypoglycemic Agents; D010078:Oxazines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000109:Acetylcholine; D005905:Glyburide; D006221:Halothane; C084963:2H-1,4-benzoxazine, 3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-pyridinyl)-, N-oxide