Kinetic transport model for cellular regulation of pH and solute concentration in the renal proximal tubule.
Kinetic transport model for cellular regulation of pH and solute concentration in the renal proximal tubule.
复制标题
肾近曲小管 pH 值和溶质浓度细胞调节的动力学转运模型。
DOI：
10.1016/s0006-3495(87)83379-9
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发表时间：
1987
影响因子：
3.4
通讯作者：
Alpern,RJ
中科院分区：
文献类型：
--
作者：
Verkman,AS;Alpern,RJ
开发了开路动力学模型，以计算近端小管细胞pH值、溶质浓度和体积对管腔或管周流体组成诱导扰动的响应的时间过程。溶质通量计算电动方程包含已知的载体饱和度，变构依赖性，和离子耦合比的条款。从细胞电中性和相等的反向跨细胞和细胞旁电流的要求迭代地确定顶侧和基底侧膜电位。该模型在一到四次迭代中收敛到膜电位，精确到0.05%。模型变量包括Na、K、HCO 3、葡萄糖、pH值（均匀CO2）、体积以及顶侧和基底侧膜电位的细胞浓度。基本模型包括Na/H、Na/葡萄糖、H和K的被动顶膜转运，Na/3 HCO 3、K、H和葡萄糖的基底侧转运，以及Na、K、Cl和HCO 3的细胞旁转运;存在顶H和基底侧3 Na/2K-ATP酶。顶端Na/H转运、基底侧Na/3 HCO 3转运和3 Na/2K-ATP酶都是饱和的。模型参数从大鼠近端小管的数据中选择。模型预测的幅度和时间过程中的细胞pH值，钠，膜电位在顶端和管周钠和HCO 3的快速变化的反应与实验非常一致。此外，该模型要求存在顶端H-ATP酶，基底外侧Na/3 HCO 3运输饱和与HCO 3，和电中性基底外侧K运输。
An open circuit kinetic model was developed to calculate the time course of proximal tubule cell pH, solute concentrations, and volume in response to induced perturbations in luminal or peritubular fluid composition. Solute fluxes were calculated from electrokinetic equations containing terms for known carrier saturabilities, allosteric dependences, and ion coupling ratios. Apical and basolateral membrane potentials were determined iteratively from the requirements of cell electroneutrality and equal opposing transcellular and paracellular currents. The model converged to membrane potentials accurate to 0.05% in one to four iterations. Model variables included cell concentrations of Na, K, HCO3, glucose, pH (uniform CO2), volume, and apical and basolateral membrane potentials. The basic model contained passive apical membrane transport of Na/H, Na/glucose, H and K, basolateral transport of Na/3HCO3, K, H, and glucose, and paracellular transport of Na, K, Cl, and HCO3; apical H and basolateral 3Na/2K-ATPases were present. Apical Na/H and basolateral K transport were regulated allosterically by pH. Apical Na/H transport, basolateral Na/3HCO3 transport, and the 3Na/2K-ATPase were saturable. Model parameters were chosen from data in the rat proximal tubule. Model predictions for the magnitude and time course of cell pH, Na, and membrane potential in response to rapid changes in apical and peritubular Na and HCO3 were in excellent agreement with experiment. In addition, the model requires that there exist an apical H-ATPase, basolateral Na/3HCO3 transport saturable with HCO3, and electroneutral basolateral K transport.