MODEL OF ION-TRANSPORT REGULATION IN CHLORIDE-SECRETING AIRWAY EPITHELIAL-CELLS - INTEGRATED DESCRIPTION OF ELECTRICAL, CHEMICAL, AND FLUORESCENCE MEASUREMENTS
MODEL OF ION-TRANSPORT REGULATION IN CHLORIDE-SECRETING AIRWAY EPITHELIAL-CELLS - INTEGRATED DESCRIPTION OF ELECTRICAL, CHEMICAL, AND FLUORESCENCE MEASUREMENTS
复制标题
DOI：
10.1016/s0006-3495(90)82385-7
复制
发表时间：
1990-08-01
影响因子：
3.4
通讯作者：
VERKMAN, AS
中科院分区：
文献类型：
--
作者：
HARTMANN, T;VERKMAN, AS
开发了电动模型来计算在气道上皮细胞中进行的实验的电参数、离子通量和细胞内离子活动的时间过程。模型变量包括细胞 [Na]、[K]、[Cl]、体积和膜电位。该模型包含顶膜 Cl、Na 和 K 电导、基底外侧膜 K 电导、Na/K/2 Cl 和 Na/Cl 同向、3 Na/2 K ATP 酶以及细胞旁电导。根据完整犬气管中报告的离子通量数据和膜电位确定转运蛋白渗透性和离子饱和度。在没有额外假设的情况下，该模型可以准确预测测量的短路电流 (lsc)、细胞电导、分压器比、开路电位以及离子替代实验中细胞离子组成的时间进程。该模型用于定量检查：(a) 转运抑制剂对 lsc 和膜电位的影响，(b) 顶端 Cl 和基底外侧 K 电导在细胞分泌中的双重作用，(c) 基底外侧同向转运蛋白是否需要 K，以及 (d) cAMP 和 Ca 依赖性信号通路对顶端 Cl 电导的调节。模型预测加深了对运输系统之间相互关系的理解，并且在许多情况下给出了令人惊讶的预测，如果没有详细的模型，这些预测并不明显。这里开发的模型可直接应用于正常和病理生理状态（如囊性纤维化和霍乱）的肾脏厚升肢、角膜、汗管和肠道中的分泌或吸收上皮细胞。
An electrokinetic model was developed to calculate the time course of electrical parameters, ion fluxes, and intracellular ion activities for experiments performed in airway epithelial cells. Model variables included cell [Na], [K], [Cl], volume, and membrane potentials. The model contained apical membrane Cl, Na, and K conductances, basolateral membrane K conductance, Na/K/2 Cl and Na/Cl symport, and 3 Na/2 K ATPase, and a paracellular conductance. Transporter permeabilities and ion saturabilities were determined from reported ion flux data and membrane potentials in intact canine trachea. Without additional assumptions, the model predicted accurately the measured short-circuit current (lsc), cellular conductances, voltage-divider ratios, open-circuit potentials, and the time course of cell ion composition in ion substitution experiments. The model was used to examine quantitatively: (a) the effect of transport inhibitors on lsc and membrane potentials, (b) the dual role of apical Cl and basolateral K conductance in cell secretion, (c) whether the basolateral symporter requires K, and (d) the regulation of apical Cl conductance by cAMP and Ca-dependent signaling pathways. Model predictions gave improved understanding of the interrelations among transporting systems and in many cases gave surprising predictions that were not obvious without a detailed model. The model developed here has direct application to secretory or absorptive epithelial cells in the kidney thick ascending limb, cornea, sweat duct, and intestine in normal and pathophysiological states such as cystic fibrosis and cholera.