Fukushima T, Hirasaki A, Jones K A, Warner D O
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
Br J Anaesth. 1996 Jun;76(6):847-53. doi: 10.1093/bja/76.6.847.
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.
早期研究表明，氟烷可能部分通过开放三磷酸腺苷敏感性钾（KATP）通道来舒张平滑肌。我们通过在器官浴系统中安装的犬气管平滑肌条上，检测氟烷与KATP通道阻滞剂格列本脲以及KATP通道开放剂YM934的相互作用，对这一假说进行了体外试验。为了检测氟烷对KATP通道任何作用的特异性，我们评估了氟烷与大电导钙激活钾通道拮抗剂四乙铵（TEA）的相互作用。实验分别在暴露于递增浓度乙酰胆碱（ACh）之前添加药物，以及在ACh产生稳定的力量增加后添加药物（ACh预收缩）的情况下进行。暴露于0.62 mmol/L的氟烷（相当于约2倍最低肺泡有效浓度）显著增加了ACh诱导收缩的半数有效浓度（ED50）（增加了0.24（标准误0.07）μmol/L）。1 mmol/L的TEA而非10 μmol/L的格列本脲显著增强了ED50的这种增加（额外增加了0.17（0.06）μmol/L）。在ACh预收缩的肌条中，TEA而非格列本脲增强了氟烷诱导的浓度依赖性舒张。用0.32 μmol/L的YM934孵育显著增加了ACh诱导收缩的ED50（从0.12（0.02）增加到0.55（0.11）μmol/L），这种增加不受暴露于0.72 mmol/L氟烷的影响。当添加到用约0.3 μmol/L的ACh预收缩的肌条中时，YM934产生浓度依赖性舒张；氟烷对这种舒张几乎没有影响。这些结果不支持氟烷部分通过开放KATP通道来舒张犬气管平滑肌这一假说。
