T. Zeuthen: Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Blegdamsvej 3C, DK2200N, Copenhagen, Denmark.
J Physiol. 2013 Oct 15;591(20):5017-29. doi: 10.1113/jphysiol.2013.261321. Epub 2013 Aug 19.
Abstract We test a novel, stochastic model of osmotic water transport in aquaporins. A solute molecule present at the pore mouth can either be reflected or permeate the pore. We assume that only reflected solute molecules induce osmotic transport of water through the pore, while permeating solute molecules give rise to no water transport. Accordingly, the rate of water transport is proportional to the reflection coefficient σ, while the solute permeability, P(S), is proportional to 1 - σ. The model was tested in aquaporins heterologously expressed in Xenopus oocytes. A variety of aquaporin channel sizes and geometries were obtained with the two aquaporins AQP1 and AQP9 and mutant versions of these. Osmotic water transport was generated by adding 20 mM of a range of different-sized osmolytes to the outer solution. The osmotic water permeability and the reflection coefficient were measured optically at high resolution and compared to the solute permeability obtained from short-term uptake of radio-labelled solute under isotonic conditions. For each type of aquaporin there was a linear relationship between solute permeability and reflection coefficient, in accordance with the model. We found no evidence for coupling between water and solute fluxes in the pore. In confirmation of molecular dynamic simulations, we conclude that the magnitude of the osmotic water permeability and the reflection coefficient are determined by processes at the arginine selectivity filter located at the outward-facing end of the pore.
摘要 我们测试了一种新型的水通过水通道蛋白渗透的随机模型。位于孔口的溶质分子要么被反射，要么渗透过孔。我们假设只有被反射的溶质分子才能诱导水通过孔的渗透运输，而渗透的溶质分子则不会引起水的运输。因此，水的运输速率与反射系数σ成正比，而溶质的渗透率 P(S) 与 1-σ成正比。该模型在非洲爪蟾卵母细胞中异源表达的水通道蛋白中进行了测试。通过使用两种水通道蛋白 AQP1 和 AQP9 及其突变体，获得了各种不同大小和几何形状的水通道蛋白。通过在外液中添加 20mM 的一系列不同大小的渗透物来产生渗透水运输。在高分辨率下通过光学方法测量渗透水的渗透率和反射系数，并与在等渗条件下用放射性标记的溶质进行短期摄取所获得的溶质渗透率进行比较。对于每种类型的水通道蛋白，溶质渗透率和反射系数之间都存在线性关系，符合该模型。我们没有发现孔内水和溶质通量之间存在耦合的证据。与分子动力学模拟的结果一致，我们得出结论，渗透压水渗透率和反射系数的大小取决于位于孔向外表面的精氨酸选择性过滤器的过程。
