VOLUME ABSORPTION IN THE RENAL PROXIMAL TUBULE

本项目将探讨音量的基本机制 肾近端小管吸收，包括驱动 水流过肾小管上皮细胞的力， 水通过它穿过上皮， 蛋白质在维持上皮结构的过程中， 水流动，并提供驱动水流出的力， 细胞间隙 所依据的技术包括 离体肾小管灌流，渗透行为观察 孤立的顶膜水泡，冷冻断裂， 离体膜的荧光膜标记研究 水泡，上皮细胞的光镜和电镜检查 分离的小管中的结构，以及分离的 近端小管的基底膜。 具体目标 是：1）测量跨上皮反射系数， 近端小管运输的主要溶质;这将是 用于确定是否出现显著的水流 2）测量渗透压; 近曲小管顶膜透水性 使用孤立的膜泡;这种渗透性是重要的 用于确定水流路径是否可以 完全细胞; 3）探索免疫诱导的 近端小管超微结构上的水流， 描述Sercine胶体对流动诱导的变化的影响， 上皮结构;这项工作将有助于确定serum的作用 蛋白质在维持近端小管结构中的作用 体积吸收; 4）为了确定 基底膜对蛋白质的依赖性和细胞膜对蛋白质的依赖性 基底膜充当半透膜， 从细胞内空间抽取液体;和5）使 将收集到的数据整合到计算机模型中， 将：a）描述水流过上皮的路径 B）描述近端小管的可能浓度 蛋白质在近端小管的细胞间隙和 在从流体中提取流体时， 上皮，和c）评估细胞间空间作为一个细胞间隙的作用。 隔室，可以帮助耦合溶质的运输， 水流过上皮 长期目标是 项目是描述体积吸收的机制， 近端小管，期望这一知识将 有助于理解体液平衡。

This project will explore the basic mechanism of volume absorption in the renal proximal tubule, including the driving forces for water flow across the tubular epithelium, the pathway by which water crosses the epithelium, and the role of serosal protein in maintaining the structure of the epithelium during water flow and in providing a force for driving water flow out of the intercellular space. The techniques to be based include the perfusion of isolated tubules, the observation of osmotic behavior of isolated apical-membrane blebs, freeze-fracture and fluorescent-membrane-marker studies of isolated membrane blebs, light and electron microscopic examination of epithelial structure in isolated tubules, and the perfusion of isolated basement membrane from proximal tubules. The specific aims are: 1) To measure the transepithelial reflection coefficients for the major solutes transported by the proximal tubule; this will be used to determine whether significant flow of water occurs between the cells of this epithelium; 2) To measure the osmotic water permeability of the apical membrane of the proximal tubule using isolated membrane blebs; this permeability is an important parameter for determining if the pathway for water flow can be entirely cellular; 3) To explore the effects of osmotically induced water flow on the ultrastructure of the proximal tubule, and to describe the effects of serosal colloid on flow-induced changes in epithelial structure; this work will help define the role of serosal protein in maintaining the structure of the proximal tubule during volume absorption; 4) To determine the permeability properties of the basement membrane to protein and the ability of the basement membrane to act as a semi-permeable membrane for abstraction of fluid from the intracellular space: and 5) To bring together the data that are collected into computer models that will: a) described the route of water flow across the epithelium of the proximal tubule, b) describe the probable concentration of protein in the intercellular space of the proximal tubule and the role that oncotic forces play in abstracting fluid from the epithelium, and c) assess the role of the intercellular space as a compartment that can aid in coupling the transport of solute and water across this epithelium. The long-range objective of this project is to describe the mechanism of volume absorption in the proximal tubule, with the expectation that this knowledge will help in understanding body fluid homeostasis.