THEORETICAL ANALYSIS OF SOLUTE AND WATER TRANSPORT

这个持续项目的总体目标是将实验 关于膜水平上的水和溶质输送到 对两者都有用的全肾功能预测模型 实验设计和病人管理。重点放在处理上 钠、钾、尿素和水分及其在细胞内的调控 机械装置。具体目标是： 1.对那些尚未建模的节段进行建模：近端直管 (PST)，降细肢(DTL)，升细肢(ATL)，远端 曲管(DCT)、连接管(CNT)、内外 髓集合管(OMCD和IMCD)。这些模型将基于 近曲小管(PCT)、粗大升肢的现有模型 亨勒氏环(TAL)、皮质集合管(CCT)和Will 包括细胞途径和细胞旁途径，以及下列途径 变量：钠、钾、氯、尿素、静水压力和电 潜力。对于某些细分市场，这些型号将包括额外的 变量H、HCO3-、HPO4-、H2P04-、NH4、NH3、Ca、Mg、葡萄糖和 可能是有机渗透分子。 2.首先将分段模型合成成循环的模型 Henle，这将被用来解释体内血流灌注数据，然后 再加上PT模型和肾小球后毛细血管模型 皮质肾单位，它将被用来解释皮质自由流动 显微穿刺术数据。 3.利用DTL、ATL和IMCD模型探索可能的新技术 肾内髓质的浓缩机制：特别是 尿素-电解液的热力学可行性及其可能的作用 共传输系统驱动电解液从ATL循环到DTL。 4.对不同肾单位段的电缆特性进行建模 细胞和细胞旁的运输过程。 5.将分段模型扩展到包括钙和镁。在这里，我们将 主要致力于开发钙处理模型，由 慢性结缔组织瘤的主细胞及其胞内钙在其调控中的作用 心尖部钠离子通透性。如果出现足够的数据库，我们还将 开发TAL处理镁的可能模型。这里有一个假设 需要检验的是，胞质镁调节K：Na：2Cl的活性 辅助传送器。

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.