THEORETICAL ANALYSIS OF SOLUTE AND WATER TRANSPORT

溶质和水运移的理论分析

• 批准号: 2138641
• 负责人: JOHN L STEPHENSON
• 金额: $ 21.94万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2138641
• 关键词: aldosterone; apical membrane; basolateral membrane; chloride channels; computer simulation; diuretics; electrical potential; electrolyte balance; excretion; glucose; hormone regulation /control mechanism; hydrostatic pressure; ion transport; kidney circulation; kidney function; mathematical model; membrane permeability; model design /development; nonblood rheology; potassium channel; renal tubular transport; scintillation cameras; sodium channel; solute; supercomputer; urea; vasopressins; water

The overall aim in this continuing project is to integrate experimental data on water and solute transport at the membrane level into a predictive model of whole kidney function that is useful in both experimental design and patient management. the focus is on the handling of Na, K, urea, and water and their control by various cellular mechanisms. Specific aims are: 1. To model those segments not yet modeled: proximal straight tubule (PST), descending thin limb (DTL), ascending thin limb (ATL), distal convoluted tubule (DCT), connecting tubule (CNT), and outer and inner medullary collecting duct (OMCD & IMCD). the models will be based on existing models of proximal convoluted tubule (PCT), thick ascending limb of Henle's loop (TAL), and cortical collecting tubule (CCT) and will include both cellular and paracellular pathways and the following variables: Na+, K+, Cl-, urea, hydrostatic pressure, and electric potential. For some segments the models will include the additional variables H+, HCO3-, HPO4--, H2P04-, NH4+, NH3, Ca++, Mg++, glucose, and possibly organic osmolytes. 2. To synthesize the segmental models first into a model of the loop of Henle, which will be used to interpret in vivo perfusion data, and then together with a model of PT and post-glomerular capillary into a model of a cortical nephron, which will be used to interpret free flow cortical micropuncture data. 3. To use the models of DTL, ATL, and IMCD to explore possible new mechanisms of concentration for the renal inner medulla: in particular the thermodynamic feasibility and possible role of urea-electrolyte cotransport systems driving electrolyte cycling from ATL to DTL. 4. To model the cable properties of the various nephron segments in terms of cellular and paracellular transport processes. 5. To extend the segmental models to include Ca++ and Mg++. Here we will focus primarily on developing a model of calcium handling by the principal cell of CCT and the role of cytosolic Ca++ in modulating its apical Na+ permeability. If a sufficient data base emerges we will also develop possible models for Mg++ handling by TAL. Here a hypothesis to be tested is that cytosolic Mg regulates activity of the K:Na:2Cl cotransporter.

这个持续项目的总体目标是整合实验性的 水和溶质在膜水平传输到一个 全肾功能的预测模型，这是有用的，在这两个 实验设计和患者管理。 重点是处理 钠，钾，尿素和水，以及它们的控制，各种细胞 机制等 具体目标是： 1.对尚未建模的节段进行建模：近端直小管 (PST)、下行薄肢（DTL）、上行薄肢（ATL）、远端 曲小管（DCT）、连接小管（CNT）、外小管和内小管 髓集合管（OMCD & IMCD）。 模型将基于 现有的近曲小管（PCT）模型，粗升支 和皮质集合管（CCT），并将 包括细胞和细胞旁途径， 变量：Na+、K+、Cl-、尿素、静水压力和电 潜力 对于某些细分市场，模型将包括额外的 变量H+、HCO 3-、HPO 4-、H2 PO 4-、NH 4+、NH3、Ca++、Mg++、葡萄糖，以及 可能是有机渗透剂。 2.为了将分段模型首先合成为环的模型， Henle，将用于解释体内灌注数据，然后 与PT模型和肾小球后毛细血管模型一起 皮质肾单位，这将被用来解释自由流动的皮质 微穿刺数据 3.利用DTL、ATL和IMCD模型，探索可能的新方法， 肾内髓质的浓度机制：特别是 尿素电解质热力学可行性及其可能作用 共转运系统驱动电解质从ATL循环到DTL。 4.为了模拟各种肾单位段的电缆特性， 细胞和细胞旁转运过程的一个重要组成部分。 5.将节段模型扩展到包括Ca++和Mg++。 这里我们将 主要集中在开发一个模型的钙处理的 CCT的主要细胞及胞浆Ca ~（++）在其调节中的作用 顶端Na+渗透性。 如果有足够的数据库，我们也将 开发TAL处理Mg++的可能模型。 这里有一个假设， 胞浆Mg对K：Na：2Cl活性的调节 协同转运蛋白