STRUCTURE OF LIPID BILAYERS AND THE EFFECTS OF GENERAL-ANESTHETICS - X-RAY AND NEUTRON-DIFFRACTION STUDY
STRUCTURE OF LIPID BILAYERS AND THE EFFECTS OF GENERAL-ANESTHETICS - X-RAY AND NEUTRON-DIFFRACTION STUDY
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DOI：
10.1016/0022-2836(79)90403-0
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发表时间：
1979-01-01
影响因子：
5.6
通讯作者：
LIEB, WR
中科院分区：
文献类型：
--
作者：
FRANKS, NP;LIEB, WR
研究了临床常用的3种吸入麻醉药(一氧化二氮、氟烷和环丙烷)对卵磷脂/胆固醇双层膜结构的影响。麻醉剂在气相中被输送到膜上，这样就可以确定临床浓度下的效果。记录了4°的高分辨X射线衍射图，并用溶胀实验进行了分析。利用H2O-2H2O交换进行了平行的中子衍射实验，并进行了分析。发展了一些方法，使我们能够获得X射线和中子结构因子的置信限。由此产生的X射线和中子散射密度分布确定了未受扰动的双层中主要分子基团的位置。特别是，高分辨率电子密度分布显示了直接归因于胆固醇分子的特征。与中子散射密度谱的比较表明，胆固醇与其羟基锚定在水/烃界面，与卵磷脂分子的脂肪酸酯基排列。显然，胆固醇分子的这种定位允许它充当质膜的厚度缓冲器。在浓度很高的全身麻醉药存在的情况下，双层显示出更多的无序性，同时保持恒定的膜厚度。在手术浓度下，在95%的置信度水平下，双层结构没有显着变化。回顾了支持全麻脂质双层假说的文献。显然，脂质双层不是全身麻醉药的主要作用部位。
The effects of 3 clinically used inhalational anesthetics (nitrous oxide, halothane and cyclopropane) on the structure of lecithin/cholesterol bilayers were studied. The anesthetics were delivered to the membranes in the gaseous phase so that effects at clinical concentrations could be determined. High resolution X-ray diffraction patterns were recorded out to 4 .ANG. and analyzed using swelling experiments. Parallel neutron diffraction experiments were performed and analyzed using H2O-2H2O exchange. Methods were developed which enabled us to obtain confidence limits for the X-ray and neutron structure factors. The resultant X-ray and neutron scattering density profiles define the positions of the principal molecular groups in the unperturbed bilayer. In particular, the high resolution electron density profiles show features directly attributable to the cholesterol molecule. A comparison with the neutron scattering density profiles shows that cholesterol is anchored with its hydroxyl group at the water/hydrocarbon interface, aligned with the fatty acid ester groups of the lecithin molecule. Apparently this positioning of the cholesterol molecule allows it to act as a thickness buffer for plasma membranes. In the presence of very high concentrations of general anesthetics, the bilayers show increased disorder while maintaining constant membrane thickness. At surgical concentrations there are no significant changes in bilayer structure at 95% confidence levels. Literature used to support the lipid bilayer hypotheses of general anesthesia was reviewed. Apparently the lipid bilayer is not the primary site of action of general anesthetics.