Chemical kinetic and diffusional limitations on bicarbonate reabsorption by the proximal tubule.
Chemical kinetic and diffusional limitations on bicarbonate reabsorption by the proximal tubule.
复制标题
近端肾小管重吸收碳酸氢盐的化学动力学和扩散限制。
DOI：
10.1016/s0006-3495(80)85048-x
复制
发表时间：
1980
影响因子：
3.4
通讯作者：
Deen,WM
中科院分区：
文献类型：
--
作者：
Wang,KW;Deen,WM
近端小管重吸收重碳酸盐是由H+分泌介导的，这是公认的，但这个过程的几个方面仍然存在争议。为了研究这些问题中的一些，我们已经开发了一个模型，允许空间变化的浓度的CO2，HCO 3-，和H2 CO 3的小管腔和细胞质内，这些物质的被动运输跨细胞膜，碳酸酐酶催化的HCO 3-和CO2的相互转化的细胞内和在管腔膜表面，和相应的未催化的反应在管腔和细胞。大多数所需的动力学和运输参数估计从文献中的物理化学数据，而细胞内的pH值和HCO 3-渗透性在基底细胞膜，发现在正常条件下是最重要的参数，进行调整，以产生重吸收率的“总CO2”（tCO 2，CO2，HCO 3-和H2 CO 3的总和）在大鼠中的测量值。我们的研究结果表明，对于正常的碳酸酐酶活性，几乎所有的tCO 2离开管腔的CO2，但CO2分压的跨上皮差异不超过约2毫米汞柱。电化学电位梯度有利于HCO 3-从细胞到管腔的大量被动回漏。在模拟碳酸酐酶抑制过程中，CO2分压的变化很小，在这种情况下，大约70%的tCO 2以H2 CO 3的形式离开管腔，其余的以CO2的形式离开管腔。预测的tCO 2重吸收率的碳酸酐酶抑制是大约正常的，在良好的协议与最近在大鼠中的测量，表明“碳酸再循环”的概念是可行的。
It is accepted that bicarbonate reabsorption in the proximal tubule is mediated by H+ secretion, but several aspects of this process have remained controversial. To examine some of these issues, we have developed a model that allows for spatial variations in the concentrations of CO2, HCO3-, and H2CO3 within the tubule lumen and cell cytoplasm, passive transport of these substances across cell membranes, carbonic anhydrase-catalyzed interconversion of HCO3- and CO2 within the cell and at the luminal membrane surface, and the corresponding uncatalyzed reactions in lumen and cell. Most of the required kinetic and transport parameters were estimated from physicochemical data in the literature, whereas intracellular pH and HCO3- permeability at the basal cell membrane, found to be the most significant parameters under normal conditions, were adjusted to yield reabsorption rates of "total CO2" (tCO2, the sum of CO2, HCO3- and H2CO3) comparable to measured values in the rat. Our results suggest that for normal carbonic anhydrase activity, almost all tCO2 leaves the lumen as CO2, yet the transepithelial differences in CO2 partial pressure does not exceed approximately 2 mm Hg. Electrochemical potential gradients favor substantial passive backleak of HCO3- from cell to lumen. Gradients in CO2 partial pressure remain small during simulated inhibition of carbonic anhydrase, with approximately 70% of tCO2 leaving the lumen as H2CO3 in this case, and the remainder as CO2. Predicted tCO2 reabsorption rates for carbonic anhydrase inhibition are approximately of normal, in good agreement with recent measurements in the rat, indicating that the concept of "carbonic acid recycling" is viable.