THEORY OF SOLUTE AND WATER TRANSPORT ACROSS EPITHELIA

制定数学模型，将渗漏上皮表示为 系统的隔间和边界膜，并允许计算机 模拟生理学中常用的实验动作， 调查 此外，该项目还负责确定和 简化或近似数学模型的分析， 用于减少实验数据。 近似值的比较 详细的计算机模拟输出的分析模型是 用于评估较简单模型的适用范围， 隔离混杂影响。 一个具体的目标是建立一个 哺乳动物近端小管模型--一个包括四个 离子种类（Na、K、Cl、HCO 3）和蛋白质结合力，允许 上皮内溶质-溶剂偶联，并跟踪 浓度和压力沿着小管长度。 这种模式的 在离体灌流小管或微穿刺中模拟实验 在灌流肾中的实验，其中管周溶液被固定 并且相对均匀。 这将是第一次尝试模拟 这种上皮的内部结构和腔液的变化 沿着小管长度。 近端水输运动力学 小管（溶质-溶剂偶联，逆渗透转运 梯度，等渗运输）将被视为与框架 先前设计用于平坦上皮片。 水的分析模型 穿过平坦上皮的流动将延伸到管状几何形状。 一 该项目的第二个方面将是对预测的审查， 电生理仿真中的综合上皮模型 实验 特别是，“电沉默”事件的影响 （离子-离子偶联，细胞肿胀）可改变细胞内电位。

Mathematical models are formulated that represent a leaky epithelium as a system of compartments and bounding membranes and permit the computer simulation of the experimental maneuvers commonly employed in physiological investigation. Further, this project undertakes the identification and analysis of simplified, or approximate, mathematical models which may be used in the reduction of experimental data. Comparison of the approximate analytical models with the output from the detailed computer simulation is used to assess the range of applicability of the simpler models and to isolate confounding influences. A specific aim is the construction of a model of mammalian proximal tubule--a model which will include the four ionic species (Na, K, C1, HCO3) and protein oncotic forces, allow for intraepithelial solute-solvent coupling, and track the changes in concentrations and pressures along the tubule length. This model will simulate experiments in isolated perfused tubules or micropuncture experiments in perfused kidneys in which the peritubular solution is fixed and relatively uniform. It will be the first attempt to model both the internal structure of this epithelium and the changes of the luminal fluid along the tubule length. The dynamics of water transport across proximal tubule (solute-solvent coupling, transport against an adverse osmotic gradient, isotonic transport) will be considered with the framework previously devised for the flat epithelial sheet. Analytic models of water flow across a flat epithelium will be extended to a tubular geometry. A second aspect of this project will be an examination of the predictions of the comprehensive epithelial models in simulations of electrophysiological experiments. In particular, the effect of "electrically silent" events (ion-ion coupling, cell swelling) may alter intracellular potentials.