Mathematical modeling of acid-base physiology.
Mathematical modeling of acid-base physiology.
复制标题
酸碱生理学的数学模型。
DOI：
10.1016/j.pbiomolbio.2015.01.003
复制
发表时间：
2015
影响因子：
3.8
通讯作者：
Boron,WalterF
中科院分区：
文献类型：
--
作者：
Occhipinti,Rossana;Boron,WalterF
摘要pH值是生命中最重要的参数之一，几乎影响细胞、组织和全身水平的每个生物过程。因此，对于细胞，调节细胞内pH（pH i）是至关重要的，对于多细胞生物体，调节细胞外pH（pH o）是至关重要的。pH i调节取决于倾向于增加pH i的质膜转运蛋白和倾向于降低pH i的其他转运蛋白的相反作用。此外，不带电物质（如CO2、NH3）和带电物质（如HCO3 −、NH4+）的被动通量会干扰pH i。这些运动不仅相互影响，而且扰乱了大量细胞内和细胞外缓冲液的平衡。因此，即使在单个细胞的水平上，酸碱反应、扩散和运输中的扰动也是如此复杂，以至于如果没有定量模型，就不可能理解它们。在这里，我们总结了一些数学模型，揭示了复杂的相互关联的事件引发的酸碱运动。然后，我们描述了一个数学模型的球形细胞，据我们所知，这是第一个能够处理大量的缓冲反应，我们的团队最近开发的模拟pH值的变化，我和pH值的变化引起的移动的酸碱当量横跨非洲爪蟾卵母细胞的质膜。最后，我们将我们的工作扩展到考虑同时CO2和HCO 3−流入细胞的影响，并设想未来的模型如何扩展到对全身pH稳态重要的其他细胞类型（例如，红细胞）或组织（例如，肾近端小管上皮）。
Abstract pH is one of the most important parameters in life, influencing virtually every biological process at the cellular, tissue, and whole-body level. Thus, for cells, it is critical to regulate intracellular pH (pH i) and, for multicellular organisms, to regulate extracellular pH (pH o). pH i regulation depends on the opposing actions of plasma-membrane transporters that tend to increase pH i, and others that tend to decrease pH i. In addition, passive fluxes of uncharged species (eg, CO 2, NH 3) and charged species (eg, HCO 3−, NH 4+) perturb pH i. These movements not only influence one another, but also perturb the equilibria of a multitude of intracellular and extracellular buffers. Thus, even at the level of a single cell, perturbations in acid-base reactions, diffusion, and transport are so complex that it is impossible to understand them without a quantitative model. Here we summarize some mathematical models developed to shed light onto the complex interconnected events triggered by acids-base movements. We then describe a mathematical model of a spherical cells—which to our knowledge is the first one capable of handling a multitude of buffer reactions—that our team has recently developed to simulate changes in pH i and pH o caused by movements of acid-base equivalents across the plasma membrane of a Xenopus oocyte. Finally, we extend our work to a consideration of the effects of simultaneous CO 2 and HCO 3− influx into a cell, and envision how future models might extend to other cell types (eg, erythrocytes) or tissues (eg, renal proximal-tubule epithelium) important for whole-body pH homeostasis.