Chung S H, Hoyles M, Allen T, Kuyucak S
Protein Dynamics Unit, Department of Chemistry, Research School of Physical Sciences, Australian National University, Canberra, A.C.T. 0200, Australia.
Biophys J. 1998 Aug;75(2):793-809. doi: 10.1016/S0006-3495(98)77569-1.
Brownian dynamics simulations have been carried out to study ionic currents flowing across a model membrane channel under various conditions. The model channel we use has a cylindrical transmembrane segment that is joined to a catenary vestibule at each side. Two cylindrical reservoirs connected to the channel contain a fixed number of sodium and chloride ions. Under a driving force of 100 mV, the channel is virtually impermeable to sodium ions, owing to the repulsive dielectric force presented to ions by the vestibular wall. When two rings of dipoles, with their negative poles facing the pore lumen, are placed just above and below the constricted channel segment, sodium ions cross the channel. The conductance increases with increasing dipole strength and reaches its maximum rapidly; a further increase in dipole strength does not increase the channel conductance further. When only those ions that acquire a kinetic energy large enough to surmount a barrier are allowed to enter the narrow transmembrane segment, the channel conductance decreases monotonically with the barrier height. This barrier represents those interactions between an ion, water molecules, and the protein wall in the transmembrane segment that are not treated explicitly in the simulation. The conductance obtained from simulations closely matches that obtained from ACh channels when a step potential barrier of 2-3 kTr is placed at the channel neck. The current-voltage relationship obtained with symmetrical solutions is ohmic in the absence of a barrier. The current-voltage curve becomes nonlinear when the 3 kTr barrier is in place. With asymmetrical solutions, the relationship approximates the Goldman equation, with the reversal potential close to that predicted by the Nernst equation. The conductance first increases linearly with concentration and then begins to rise at a slower rate with higher ionic concentration. We discuss the implications of these findings for the transport of ions across the membrane and the structure of ion channels.
已进行布朗动力学模拟，以研究在各种条件下跨模型膜通道流动的离子电流。我们使用的模型通道有一个圆柱形跨膜段，其两侧连接到悬链前庭。与通道相连的两个圆柱形储液器含有固定数量的钠离子和氯离子。在100 mV的驱动力下，由于前庭壁对离子呈现的排斥介电力，通道实际上对钠离子不可渗透。当两圈偶极子，其负极面向孔腔，放置在收缩通道段的上方和下方时，钠离子穿过通道。电导率随着偶极子强度的增加而增加，并迅速达到最大值；偶极子强度的进一步增加不会进一步增加通道电导率。当仅允许那些获得足够大动能以克服势垒的离子进入狭窄的跨膜段时，通道电导率随势垒高度单调降低。这个势垒代表了模拟中未明确处理的离子、水分子与跨膜段蛋白质壁之间的相互作用。当在通道颈部放置2 - 3 kTr的阶跃势垒时，模拟得到的电导率与从乙酰胆碱通道获得的电导率紧密匹配。在没有势垒的情况下，对称溶液得到的电流 - 电压关系是欧姆性的。当3 kTr势垒存在时，电流 - 电压曲线变为非线性。对于不对称溶液，该关系近似于戈德曼方程，反转电位接近能斯特方程预测的值。电导率首先随浓度线性增加，然后随着离子浓度升高开始以较慢速率上升。我们讨论了这些发现对离子跨膜运输和离子通道结构的影响。
