Department of Nephrology, University Hospital of Lund, Lund, Sweden.
Am J Physiol Renal Physiol. 2013 Mar 15;304(6):F781-7. doi: 10.1152/ajprenal.00621.2012. Epub 2013 Jan 9.
In the current study we explore the electrostatic interactions on the transport of anionic Ficoll (aFicoll) vs. neutral Ficoll (nFicoll) over the glomerular filtration barrier (GFB) modeled as a charged fiber matrix. We first analyze experimental sieving data for the rat glomerulus, and second, we explore some of the basic implications of a theoretical model for the electrostatic interactions between a charged solute and a charged fiber-matrix barrier. To explain the measured difference in glomerular transport between nFicoll and aFicoll (Axelsson J, Sverrisson K, Rippe A, Fissell W, Rippe B. Am J Physiol 301: F708-F712, 2011), the present simulations demonstrate that the surface charge density needed on a charged fiber matrix must lie between -0.005 C/m(2) and -0.019 C/m(2), depending on the surface charge density of the solute. This is in good agreement with known surface charge densities for many proteins in the body. In conclusion, the current results suggest that electrical charge makes a moderate contribution to glomerular permeability, while molecular size and conformation seem to be more important. Yet, the weak electrical charge obtained in this study can be predicted to nearly totally exclude albumin from permeating through "high-selectivity" pathways in a charged-fiber matrix of the GFB.
在当前的研究中,我们探索了带负电荷的菲可(aFicoll)相对于中性菲可(nFicoll)在肾小球滤过屏障(GFB)中运输的静电相互作用,该模型被视为带电荷的纤维基质。我们首先分析了大鼠肾小球的实验筛分数据,其次,我们探讨了一个理论模型中关于带电荷溶质和带电荷纤维基质屏障之间静电相互作用的一些基本含义。为了解释在 nFicoll 和 aFicoll 的肾小球转运中测量到的差异(Axelsson J、Sverrisson K、Rippe A、Fissell W、Rippe B. Am J Physiol 301: F708-F712, 2011),本模拟表明,带电荷纤维基质所需的表面电荷密度必须介于-0.005 C/m(2)和-0.019 C/m(2)之间,具体取决于溶质的表面电荷密度。这与体内许多蛋白质的已知表面电荷密度非常吻合。总之,目前的结果表明,电荷对肾小球通透性有适度的贡献,而分子大小和构象似乎更为重要。然而,在这项研究中获得的微弱电荷可以预测白蛋白几乎完全不能通过 GFB 带电荷纤维基质中的“高选择性”途径渗透。