Barry Peter H
School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Cell Biochem Biophys. 2006;46(2):143-54. doi: 10.1385/CBB:46:2:143.
Measurements of anion-cation permeability ratios (e.g., PCl/PNa) are most readily made by measuring changes in zero-current reversal potential when the salt concentration on one side of the membrane (e.g., external NaCl) is decreased. This is particularly useful for measuring changes in ion selectivity in wild-type and mutant channels, such as those of the ligand-gated ion channel superfamily, and has shown that many of these channels have a significant permeability to counter-ions. One Brownian dynamics study of ion permeation through such narrow ion channels failed to observe such counter-ion movement, although later, another Brownian dynamics study did observe counter-ion movement through simulations of the same channels. The question has been raised as to the reliability of such reversal potential measurements for determining permeability ratios, particularly given the use of an equation such as the Goldman-Hodgkin-Katz (GHK) equation, which is often used to calculate such ratios. A new derivation of the GHK equation in terms of activity coefficients is also included. The application of irreversible thermodynamics will be shown to qualitatively support the reliability of such experimental anion-cation permeability values derived from reversal potential measurements. It will then be shown that for such zero-current situations, different electrodiffusion models, with very different underlying assumptions, produce almost identical relative permeabilities (and reversal potentials). Finally, the results of the two Brownian dynamics simulation studies and the relationship between reversal potentials and relative permeability will be discussed.
通过测量膜一侧（如外部氯化钠）盐浓度降低时零电流反转电位的变化，最容易测量阴离子 - 阳离子渗透率比值（例如，PCl/PNa）。这对于测量野生型和突变型通道（如配体门控离子通道超家族的通道）的离子选择性变化特别有用，并且已经表明许多这些通道对反离子具有显著的渗透性。一项关于离子通过此类狭窄离子通道渗透的布朗动力学研究未能观察到这种反离子运动，尽管后来另一项布朗动力学研究通过对相同通道的模拟确实观察到了反离子运动。关于这种反转电位测量用于确定渗透率比值的可靠性问题已经被提出，特别是考虑到使用了诸如戈德曼 - 霍奇金 - Katz（GHK）方程这样的方程来计算此类比值。还包括了根据活度系数对GHK方程的新推导。将展示不可逆热力学的应用定性地支持了从反转电位测量得出的此类实验阴离子 - 阳离子渗透率值的可靠性。然后将表明，对于此类零电流情况，具有非常不同基本假设的不同电扩散模型产生几乎相同的相对渗透率（和反转电位）。最后，将讨论两项布朗动力学模拟研究的结果以及反转电位与相对渗透率之间的关系。
