Krawczyk J, Cukierman S
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
Biochim Biophys Acta. 1991 Mar 18;1063(1):60-6. doi: 10.1016/0005-2736(91)90353-a.
The effects of the polyene antibiotic filipin on the conductance and permeability of planar lipid bilayers were investigated under voltage-clamp conditions. The membrane conductance of lipid bilayers containing no cholesterol was not affected by filipin. In the presence of cholesterol containing lipid bilayers, filipin induced a 10(4)-10(5)-fold increase in transmembrane conductance. This conductance increase was dependent on the ionic species present in solution, decreasing in the following order: GCsCl greater than GNaAc greater than GKCl greater than GNaCl greater than CaCl2 greater than GNa2SO4 greater than GBaCl2 greater than GMgCl2. Reversal potential measurements in simple biionic conditions revealed the following relative permeability sequence: PK greater than PCl greater than PNa approximately Pac approximately PBa greater than PCs greater than PMg approximately PCa greater than Psulphate. The filipin-sterol mediated increase in membrane conductance was independent of the membrane potential. The increase in membrane current following a step alteration in membrane potential occurred instantaneously and had no dependence on the previous value of the holding membrane potential. We propose that the filipin-sterol complex forms ion channels in lipid membranes. These channels are found in a single configuration (open state) and select preferentially monovalent cations or anions over divalent ions. Our experimental results are discussed in relation to the effects of other polyene antibiotics on the membrane permeability, and also in relation to experimental problems previously reported with the use of filipin in planar lipid bilayers.
在电压钳制条件下，研究了多烯抗生素制霉菌素对平面脂质双层膜电导和通透性的影响。不含胆固醇的脂质双层膜的膜电导不受制霉菌素影响。在含有胆固醇的脂质双层膜存在时，制霉菌素可使跨膜电导增加10^4 - 10^5倍。这种电导增加取决于溶液中存在的离子种类，其递减顺序为：GCsCl＞GNaAc＞GKCl＞GNaCl＞CaCl2＞GNa2SO4＞GBaCl2＞GMgCl2。在简单双离子条件下的反转电位测量揭示了以下相对通透性顺序：PK＞PCl＞PNa≈Pac≈PBa＞PCs＞PMg≈PCa＞Psulphate。制霉菌素 - 甾醇介导的膜电导增加与膜电位无关。膜电位阶跃变化后膜电流的增加瞬间发生，且与钳制膜电位的先前值无关。我们提出制霉菌素 - 甾醇复合物在脂质膜中形成离子通道。这些通道以单一构型（开放状态）存在，并且优先选择单价阳离子或阴离子而非二价离子。我们结合其他多烯抗生素对膜通透性的影响以及先前报道的在平面脂质双层膜中使用制霉菌素时的实验问题，对我们的实验结果进行了讨论。
