VOLUME ABSORPTION IN THE RENAL PROXIMAL TUBULE

这个项目将探索体积的基本机制 肾近端小管的吸收，包括驱动 水流过肾小管上皮的作用力，这是 水穿过上皮的方式，以及浆膜的作用 蛋白质在维持上皮细胞结构中的作用 水的流动和提供驱使水流出的力量 细胞间的空间。将基于的技术包括 离体肾小管灌流及渗透行为的观察 隔离的根尖膜滤过泡，冷冻骨折和 离体膜的荧光膜标记研究 上皮细胞气泡、光镜和电子显微镜检查 在离体管中的结构，以及离体管的灌流 基底膜来自近端小管。具体目标 包括：1)测量跨上皮反射系数 通过近端小管运输的主要溶质；这将是 用于确定是否发生显著的水流 2)测量渗透压 近端小管顶膜透水性的研究 使用隔离的膜泡；这种渗透性是一个重要的 用于确定水流路径是否可以 3)探讨渗透压诱导的影响。 水对近端小管超微结构的影响 描述浆膜胶体对血流诱导的血流变化的影响。 上皮结构；这项工作将有助于确定浆膜的作用 蛋白质在维持近端小管结构中的作用 体积吸收；4)测定材料的渗透性 基底膜对蛋白质和蛋白质的能力 基底膜作为半透膜用于 从细胞间隙提取液体：和5)带来 将收集到的计算机模型中的数据汇总在一起 威尔：A)描述了流经上皮的水流路线 对近端小管，b)描述可能的浓度 近端小管细胞间隙中的蛋白质和 肿瘤力在提取液体中所起的作用 以及c)评估细胞间隙作为一种 可以帮助耦合溶质和 水穿过这个上皮组织。这样做的长期目标是 项目的目的是描述材料的体积吸收机制。 近端小管，期望这一知识将 有助于了解体液动态平衡。

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.