Krahn T A, Weinstein A M
Department of Physiology and Biophysics, Cornell University Medical College, New York, New York 10021, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):F344-55. doi: 10.1152/ajprenal.1996.270.2.F344.
A mathematical model of the brush border of the proximal tubule (T. A. Krahn, P. S. Aronson, and A. M. Weinstein. Bull. Math. Biol, 56: 459-490, 1994) has been extended by the inclusion of CO2 and H2CO3 as diffusible species and by the inclusion of finite rate constants for the hydration of CO2. This permits the simulation of carbonic anhydrase (CA) activity and its inhibition. We confirm the result of our previous study, which is that, in the presence of CA, the unstirred layer has only a modest effect on the observed formic acid permeability. CA inhibition results in disequilibrium pH gradients, and the effect of these gradients on formic acid permeability depends on the presence of other membrane transport proteins. We also examined the impact of CA activity on the flux of total CO2 through the brush border. Under physiological conditions, CA inhibition depressed NaHCO3 reabsorption through the brush border by interfering with the HCO3(-)-facilitated diffusion of CO2. However, the determination of brush-border CO2 permeability, using an imposed CO2 gradient, was relatively uninfluenced by CA activity. Finally, we inserted a kinetic representation of the Na+/H+ exchanger into the brush-border model. Even when luminal and cytosolic diffusion coefficients were increased 1,000-fold, there was no effect on brush-border Na+ flux. This suggests that variations in the unstirred layer cannot be responsible for the flow dependence of Na+ reabsorption.
近端小管刷状缘的数学模型（T. A. 克拉恩、P. S. 阿隆森和A. M. 温斯坦。《数学生物学公报》，56: 459 - 490，1994）通过纳入二氧化碳和碳酸作为可扩散物质以及纳入二氧化碳水合的有限速率常数得到了扩展。这使得能够模拟碳酸酐酶（CA）的活性及其抑制作用。我们证实了我们先前研究的结果，即在存在CA的情况下，未搅动层对观察到的甲酸通透性只有适度影响。CA抑制导致pH梯度失衡，这些梯度对甲酸通透性的影响取决于其他膜转运蛋白的存在。我们还研究了CA活性对通过刷状缘的总二氧化碳通量的影响。在生理条件下，CA抑制通过干扰HCO₃⁻促进的二氧化碳扩散降低了通过刷状缘的NaHCO₃重吸收。然而，使用施加的二氧化碳梯度测定刷状缘二氧化碳通透性相对不受CA活性的影响。最后，我们将Na⁺/H⁺交换体的动力学表示插入到刷状缘模型中。即使管腔和胞质扩散系数增加1000倍，对刷状缘Na⁺通量也没有影响。这表明未搅动层的变化不可能是Na⁺重吸收流量依赖性的原因。
