Alamethicin channel conductance modified by lipid charge

Alamethicin channel conductance modified by lipid charge
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DOI:
10.1007/s002490100145
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发表时间:
2001-08-01
影响因子:
2
通讯作者:
Bezrukov, SM
Bezrukov, SM
中科院分区:
生物学4区
文献类型:
--
作者:
Aguilella, VM;Bezrukov, SM

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膜表面电荷通过改变电位和重新分配离子通道附近的离子组成来改变离子通道的电导。我们研究了脂质电荷对多肽抗生素丙甲霉素在平面脂质双层中形成的多态通道电导的影响。在两种脂质中测量通道电导:中性二油酰磷脂酰乙醇胺(DOPE)和带负电荷的二油酰磷脂酰丝氨酸(DOPS)。DOPS的电荷状态由膜浴溶液的pH操纵。我们发现在高盐浓度下(例如,2 M NaCl),脂质电荷的影响低于我们测量的准确度。然而,当膜基溶液中的盐浓度降低时,表面电荷本身表现为对应于最小导电丙甲霉素聚集体的前两个通道水平的电导增加。我们的分析表明,盐和pH值依赖的表面电荷效应可以合理化内的非线性泊松-玻尔兹曼方法。鉴于中性脂质中的通道电导,我们使用不同的程序来解释表面电荷(例如,在通道孔上引入平均值并考虑Na+吸附到DOPS头),但只有一个可调节参数:从最近的脂质电荷到通道口中心的有效距离。我们表明,这个距离变化0.3-0.4 nm时,从最小的导电聚合物(LO级)到下一个较大的(LI级)的通道过渡。这一结论与丙甲霉素聚集的简单几何模型雅阁。
The membrane surface charge modifies the conductance of ion channels by changing the electric potential and redistributing the ionic composition in their vicinity. We have studied the effects of lipid charge on the conductance of a multi-state channel formed in planar lipid bilayers by the peptide antibiotic alamethicin. The channel conductance was measured in two lipids: in a neutral dioleoylphosphatidylethanolamine (DOPE) and a negatively charged dioleoylphosphatidylserine (DOPS). The charge state of DOPS was manipulated by the pH of the membrane-bathing solution. We find that at high salt concentrations (e.g., 2 M NaCl) the effect of the lipid charge is below the accuracy of our measurements. However, when the salt concentration in the membrane-ba thing solution is decreased , the surface charge manifests itself as an increase in the conductance of the first two channel levels that correspond to the smallest conductive alamethicin aggregates. Our analysis shows that both the salt and pH dependence of the surface charge effect can be rationalized within the nonlinear Poisson-Boltzmann approach. Given channel conductance in neutral lipids, we use different procedures to account for the surface charge (e.g., introduce averaging over the channel aperture and take into account Na+ adsorption to DOPS heads), but only one adjustable parameter: an effective distance from the nearest lipid charge to the channel mouth center. We show that this distance varies by 0.3-0.4 nm upon channel transition from the minimal conducting aggregate (level LO) to the next larger one (level LI). This conclusion is in accord with a simple geometrical model of alamethicin aggregation.