Ibragimova V Kh, Alieva I N, Aliev D I
Institute of Radiation Problems, National Academy of Sciences of Azerbaijan Republic, Baku.
Tsitologiia. 2003;45(8):804-11.
Effects induced in bilayer lipid membranes by amphotericin B and its alkyl derivatives was analysed. Inactivation of the antibiotic-dependent multichannel membrane conductance was discovered. Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane. At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to the transient. We suggest that the phenomenon of biphasic kinetics of membrane conductance is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores combine to build up a conducting channels-conducting 2, and the conducting channels are disassemled to monomers and nonconducting self-associated forms inside the membrane-disassembled state (nonconducting 3). To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form. The existence of definite monomers and nonconducting self-associated forms of amphotericin B molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of amphotericin B and its alkyl derivatives, when the antibiotics are washed out from aqueous medium. Equilibrium between different antibiotic assemblies inside the membrane was demonstrated by the kinetics of conductance decrease following washing the antibiotic. Using circular dichroism measurements, we observed that amphotericin B alkyl derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes. The phenomenon of biophasic kinetics was observed only in the cholesterol-containing membrane. The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic concentration.
分析了两性霉素B及其烷基衍生物对双层脂质膜的影响。发现了依赖抗生素的多通道膜电导的失活。膜电导率的动力学显示取决于膜中抗生素的浓度。在10^(-8)至10^(-7)M的浓度之间，产生的电导似乎是瞬态的。我们认为膜电导双相动力学现象是膜中多烯通道连续转变的结果：半孔在膜非导电状态1的两侧组装；两个半孔结合形成导电通道——导电状态2，并且导电通道在膜内分解为单体和非导电自缔合形式——分解状态（非导电状态3）。为了解释诱导电导的瞬态特性，有人提出，以自缔合形式存在于溶液中的抗生素与膜结合并形成孔，然后以非活性单体形式在双层中解离。当从水介质中洗去抗生素时，根据两性霉素B及其烷基衍生物的脂质膜的动力学电导依赖性，估计了膜内两性霉素B分子确定的单体和非导电自缔合形式的存在。通过洗涤抗生素后电导降低的动力学证明了膜内不同抗生素聚集体之间的平衡。使用圆二色性测量，我们观察到两性霉素B烷基衍生物呈自缔合形式，易于在含胆固醇的膜上形成孔。双相动力学现象仅在含胆固醇的膜中观察到。用麦角固醇替代膜胆固醇可在任何抗生素浓度下提供膜电导的单调动力学。
