The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B.
The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B.
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多烯抗生素Nystatin和两性霉素B中诱导的薄脂质膜诱导的离子通透性。
DOI：
10.1085/jgp.56.1.100
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发表时间：
1970-07
影响因子：
3.8
通讯作者：
Krespi, V
中科院分区：
文献类型：
--
作者：
Cass, A;Finkelstein, A;Krespi, V
制霉菌素和两性霉素B对薄（<100 A）脂质膜的作用特点：(A)微摩尔量使膜电导从10-8增加到10-2 Ω-1 cm-2以上；(b)这种膜具有（非理想的）阴离子选择性，并根据大小区分阴离子；(c)膜固醇是起作用所必需的；(d)抗生素在膜两侧的存在强烈促进作用；(e)电导与抗生素浓度的幂成正比；(f)当温度升高10°C时，电导率降低~ 104倍；(g)抗生素作用的动力学也对温度非常敏感；(h)离子选择性在3 ~ 10之间与pH无关，但(i)活性在高pH下可逆丧失；(j)甲酯衍生物是完全活性的；n -乙酰基和n -琥珀基衍生物是无活性的；(k)膜分离不同盐溶液时的电流-电压特性是非线性的。这些特性与缬霉素的特性形成对比。观察结果(a) - (g)表明，来自膜两侧的多烯和甾醇聚集体相互作用，形成水孔；这些孔隙不是静态的，而是不断地分解（融化）和改造。阴离子选择性的机理尚不清楚。(h) - (j)表明- nh3 +对活性很重要；它可能不负责选择性，特别是因为四种多烯抗生素，每个含有两个nh3 +基团，诱导理想的阳离子选择性。制霉菌素和两性霉素B中的许多羟基可能是阴离子选择性的原因。多烯类抗生素对薄脂膜的作用与其对生物膜的作用一致。
Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10-8 to over 10-2 Ω-1 cm-2; (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases ∼104 times for a 10°C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)–(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Mechanism of anion selectivity is obscure. Observations (h)–(j) suggest—NH3 + is important for activity; it is probably not responsible for selectivity, particularly since four polyene antibiotics, each containing two—NH3 + groups, induce ideal cation selectivity. Possibly the many hydroxyl groups in nystatin and amphotericin B are responsible for anion selectivity. The effects of polyene antibiotics on thin lipid membranes are consistent with their action on biological membranes.