Reverification of the mechanistic membrane effects of anesthetics : Interactions with biomembrane rafts and specific membrane lipids

除了传统的麻醉剂与受体和通道特异性结合的机制外，我们根据最新的生物膜结构和功能理论，重新验证了麻醉剂可能与生物膜相互作用以发挥临床有用和不良作用的机制假设。膜脂筏与麻醉剂的相关性至少在它们对筏样模型膜的影响方面是值得怀疑的。然而，麻醉剂的结构依赖性相互作用与仿生膜组成的特定的脂质（胆固醇和阴离子磷脂）和它们的相互作用的效力之间的歧视，甚至立体异构体。这些结果支持麻醉剂的膜相互作用为作用方式。

Apart from the conventional mechanism in which anesthetics specifically bind to receptors and channels, we reverified the mechanistic hypothesis that anesthetics may interact with biomembranes to exert clinically useful and adverse effects based on the latest structural and functional theory about biomembranes. The relevance of membrane lipid rafts to anesthetics was questionable at least in their effects on raft-like model membranes. However, anesthetics structure-dependently interacted with biomimetic membranes consisting of specific lipids (cholesterol and anionic phospholipids) and their interacting potencies were discriminated even between stereoisomers. These results support the membrane interaction of anesthetics as the mode of action.