Revisiting lipid - general anesthetic interactions (I): Thinned domain formation in supported planar bilayers induced by halothane and ethanol

Revisiting lipid - general anesthetic interactions (I): Thinned domain formation in supported planar bilayers induced by halothane and ethanol
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DOI:
10.1139/v04-23
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发表时间:
2004-07-01
影响因子:
1.1
通讯作者:
Cramb, DT
Cramb, DT
中科院分区:
化学4区
文献类型:
--
作者:
Leonenko, ZV;Cramb, DT

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麻醉的分子机制是一个长期存在的问题。麻醉剂是靶向蛋白质还是改变膜的性质,还是两者兼而有之?我们使用变温磁A/C模式原子力显微镜(AFM)研究了挥发性麻醉剂氟烷和乙醇与由1,2-二油酰-sn-3-甘油-3-磷酸胆碱(DOPC)、二油酰三甲铵丙烷(DOTAP)或1,2-二棕榈酰-sn-3-甘油-3-磷酸胆碱(DPPC)支撑的平面双层(SPB)制成的模型膜的相互作用。我们发现,氟烷或乙醇的掺入诱导双层结构的变化。这些化合物导致L-α双层的厚度减小(整体上或在域中),并在L-β相双层中形成具有减小厚度的域。我们建议,麻醉诱导的面积增加每脂质驱动局部链紊乱,从而促进局部相变。将掺入氟烷或乙醇的SPB的特征与无麻醉剂SPB的L-α和L-β相的特征进行比较。
A long-standing question in anesthesia is that of the molecular mechanism. Do anesthetics target proteins or change membrane properties or both? We used temperature-dependent magnetic A/C mode atomic force microscopy (AFM) to study interaction of the volatile anesthetics halothane and ethanol with model membranes made from supported planar bilayers (SPBs) of 1,2-dioleoyl-sn-3-glycero-3-phosphocholine (DOPC), dioleoyltrimethylammonium propane (DOTAP), or 1,2-dipalmitoyl-sn-3-glycero-3-phosphocholine (DPPC). We found that the incorporation of halothane or ethanol induces structural changes in the bilayer. These compounds cause thickness reduction in L-alpha bilayers (either globally or in domains) and the formation of domains with reduced thickness in L-beta phase bilayers. We propose that an anesthetic-induced increased area per lipid drives local chain disorder, thus promoting local phase change. The characteristics of SPBs with halothane or ethanol incorporated were compared with characteristics of the L-alpha and L-beta phases of anesthetic-free SPBs.