An effect of antibiotic amphotericin B on ion transport across model lipid membranes and tonoplast membranes
An effect of antibiotic amphotericin B on ion transport across model lipid membranes and tonoplast membranes
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DOI：
10.1016/j.bcp.2005.06.001
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发表时间：
2005-09-01
影响因子：
5.8
通讯作者：
Gruszecki, WI
中科院分区：
文献类型：
--
作者：
Herec, M;Dziubinska, H;Gruszecki, WI
将pH敏感的荧光探针三磺酸吡拉林（piranine trisulfonate）包埋在蛋黄卵磷脂形成的单层脂质体中，研究了多烯抗生素阿替霉素B（AmB）对质子跨膜转运的影响。荧光监测的脂质囊泡内的pH值变化的时间依赖性，突然酸化的脂质体悬浮液，进行了分析，在双指数动力学。看来，相对于脂质，添加3 mol %的AmB显著增加了质子传输的快速组分的速率常数（从（60至149）x 10（-3）s（-1）变化），并降低了慢速组分的速率常数（从（11至5）x 10（-3）s（-1）变化）。掺入0.1 mol % AmB导致两个参数降低（分别降低至（33和2）x 10（-3）s（-1））。跨脂质膜的质子转移速率的增加被解释为与AmB在较高浓度的药物或膜结构的非特异性不稳定下形成膜通道有关。在不可能形成AmB分子结构的低浓度下，抗生素分子相对于膜平面水平取向，并使膜更致密且离子渗透性更低。脂质相中存在浓度为3mol%及以下的固醇（胆固醇、麦角固醇和胆固醇二聚体），会降低质子跨膜转移的速率常数，但不会显着影响AmB对离子转运的影响。用膜片钳技术监测，从圆锥锥头霉分离的液泡膜的浴液中存在的AmB在1 × 10~（-7）至3.6 × 10~（-5）的浓度范围内对离子电流没有显著影响。(c)2005年爱思唯尔公司All rights reserved.
A pH sensitive fluorescence probe piranine trisulfonate, entrapped inside small unilamellar liposomes formed with egg yolk phosphatidylcholine, was applied to investigate effect of polyene antibiotic amphotericin B (AmB) on proton transport across lipid membranes. Time dependencies of fluorescence-monitored pH changes inside lipid vesicles, upon sudden acidification of the liposome suspension, were analyzed in terms of two-exponential kinetics. It appears that addition of AmB at 3 mol%, with respect to lipid, considerably increases the rate constant of the fast component of proton transport (a change from (60 to 149) x 10(-3) s(-1)) and decreases the rate constant of the slow component (a change from (11 to 5) x 10(-3) s(-1)). Incorporation of 0.1 mol% AmB results in the decrease of both parameters (to (33 and 2) x 10(-3) s(-1), respectively). The increase in the rate of proton transfer across the lipid membrane is interpreted as related to the formation of membrane channels by AmB, at higher concentration of the drug or nonspecific destabilization of the membrane structure. At low concentrations, at which formation of molecular structures of AmB is not possible, the antibiotic molecules are oriented horizontally with respect to the plane of the membrane and act in making the membrane more compact and less permeable to ions. The presence of sterols (cholesterol, ergosterol and cholesterol dimer) in the lipid phase, in the concentration 3 mol% and lower, decreased the rate constants of proton transfer across the membranes but did not influence significantly the effect of AmB on the ion transport. The presence of AmB in the bathing solutions of tonoplast membranes isolated from Conocephalum conicum at the concentrations range 1 x 10(-7) to 3.6 x 10(-5) does not influence considerably the ion current, as monitored by means of the patch-clamp technique. (c) 2005 Elsevier Inc. All rights reserved.