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重构脂质双分子层中的大电导胆固醇-两性霉素B通道。

Large-conductance cholesterol-amphotericin B channels in reconstituted lipid bilayers.

作者信息

Yilma Solomon, Cannon-Sykora Jennifer, Samoylov Alexandre, Lo Ting, Liu Nangou, Brinker C Jeffrey, Neely William C, Vodyanoy Vitaly

机构信息

Department of Anatomy, Physiology and Pharmacology, Auburn University, 109 Greene Hall, Auburn, AL 36849, USA.

出版信息

Biosens Bioelectron. 2007 Feb 15;22(7):1359-67. doi: 10.1016/j.bios.2006.06.004. Epub 2006 Jul 13.

DOI:10.1016/j.bios.2006.06.004
PMID:16842986
Abstract

The antimycotic activity of amphotericin B (AmB) depends on its ability to make complexes sterols to form ion channels that cause membrane leakage. To study this phenomenon, surface pressure (pi) as a function of surface area (A) and pi-A hysteresis were measured in monolayers of AmB-cholesterol mixtures on the water-air interface. The most stable monolayers were produced from molecules of AmB and cholesterol with 2:1 stoichiometry. At this ratio, AmB and cholesterol interact to form ion channels in lipid bilayers with millisecond dwell times and conductances of 4-400 pS. The AmB-cholesterol complexes assemble in three, four, etc., subunit aggregates to form ion channels of diverse and large-conductances. Their I-V characteristics were linear over a range of +/-200 mV. The channel currents were inhibited by the addition of tetraethylammonium (TEA), potassium channel blocker, to the cis-side of the membrane. Likewise, AmB-cholesterol complexes reconstituted in membrane-coated nanoporous silicon dioxide surfaces showed single channel behavior with large amplitudes at various voltages. Large-conductance ion channels show great promise for use in biosensors on solid supports.

摘要

两性霉素B(AmB)的抗真菌活性取决于其与甾醇形成复合物以形成导致膜渗漏的离子通道的能力。为了研究这一现象,在水-空气界面上的AmB-胆固醇混合物单分子层中测量了表面压力(π)作为表面积(A)的函数以及π-A滞后现象。最稳定的单分子层是由化学计量比为2:1的AmB和胆固醇分子形成的。在此比例下,AmB和胆固醇相互作用在脂质双层中形成离子通道,其驻留时间为毫秒级,电导为4-400 pS。AmB-胆固醇复合物组装成三个、四个等亚基聚集体,形成具有不同且大电导的离子通道。它们的I-V特性在+/-200 mV范围内呈线性。通过向膜的顺式侧添加钾通道阻滞剂四乙铵(TEA),通道电流受到抑制。同样,在膜包覆的纳米多孔二氧化硅表面重构的AmB-胆固醇复合物在不同电压下表现出单通道行为且幅度较大。大电导离子通道在用于固体支持物上的生物传感器方面显示出巨大的应用前景。

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