A MOLECULAR MODEL OF MEMBRANE EXCITABILITY
A MOLECULAR MODEL OF MEMBRANE EXCITABILITY
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DOI：
10.1002/jss.400020504
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发表时间：
1974-01-01
期刊：
影响因子：
--
通讯作者：
MUELLER P
中科院分区：
文献类型：
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作者：
BAUMANN G;MUELLER P
阿拉美辛、莫那霉素或EIM可诱导脂双层的电兴奋性。电压依赖门控显示了在可兴奋细胞中观察到的所有特征，其基本特征可用Hodgkin-Huxley方程定量描述。它假设在没有电场的情况下，形成通道的分子位于膜的表面。施加的电势使它们从表面倾斜到双层的碳氢化合物区域。一旦到达这个位置，分子就会横向扩散并形成聚集体，作为离子流动的通道。在丙氨西林的情况下，我们假设分子形成一个细长的椭球体，一端有两个谷氨酸残基，另一端是一个金属离子，与多肽羰基氧合四到五次配位。外加磁场将阳离子端通过膜拉到另一边，而谷氨酸残基则将另一端固定在原始表面上。分子现在跨越膜和聚集体，形成寡聚体通道，其中大多数多肽羰基朝向中心，甲基朝向外部。单体和二聚体不传导，单个通道可能具有不同的电导值，具体取决于聚集体中单体的数量和所产生的通道直径。这一过程的定量描述与观察到的选通动力学、选通电流和单通道电导增量相匹配。在没有额外假设的情况下，失活直接发生在聚集过程中，因为在适当的速率常数下，平均聚合度和开放通道的数量在时间上经历了最大值。该模型也可以适用于更高细胞的激发过程。
Alamethicin, monazomycin, or EIM induce electrical excitability in lipid bilayers. The voltage‐dependent gating displays all the characteristics observed in excitable cells and its basic features can be quantitatively described by the Hodgkin‐Huxley equations.A common molecular mechanism of membrane excitation has been postulated. It assumes that in the absence of an electrical field the channel‐forming molecules lie at the surface of the membrane. An applied potential tilts them from the surface into the hydrocarbon region of the bilayer. Once in this position the molecules diffuse laterally and form aggregates which act as channels for the flow of ions.In the case of alamethicin we assume that the molecule forms an elongated ellipsoid with two glutamic residues at one end, and a metal ion in four‐ or five‐fold coordination with peptide carbonyl oxygens at the other. An applied field pulls the cationic end through the membrane to the other side, while the glutamic residues hold the other end attached to the original surface. The molecules now span the membrane and aggregate, forming oligomeric channels in which most of the peptide carbonyls face toward the center, and the methyl groups outward.Monomers and dimers do not conduct and an individual channel can have different conductance values depending on the number of monomers in the aggregate and the resulting channel diameter. A quantitative description of this process matches observed gating kinetics, gating currents, and the single channel conductance increments. Without additional assumptions, inactivation follows directly from the aggregation process because with proper rate constants, the average degree of polymerization and therefore number of open channels goes through a maximum in time.The model may also apply to the excitation process of higher cells.