Modelling intracellular H(+) ion diffusion.
Modelling intracellular H(+) ion diffusion.
复制标题
DOI：
10.1016/s0079-6107(03)00027-0
复制
发表时间：
2003-10
影响因子：
3.8
通讯作者：
P. Swietach;M. Zaniboni;A. K. Stewart;A. Rossini;K. Spitzer;R. Vaughan-Jones
中科院分区：
文献类型：
--
作者：
P. Swietach;M. Zaniboni;A. K. Stewart;A. Rossini;K. Spitzer;R. Vaughan-Jones
细胞内pH是细胞功能的重要调节剂，由质膜蛋白调节，质膜蛋白将H+或其等价物转运入细胞或从细胞中转运出。pH值也通过对细胞质蛋白质、寡肽和其他溶质的高容量内在缓冲以及外源性CO2/HCO 3 −（碳酸）缓冲来稳定。由于这些缓冲液的迁移率低于H+离子，因此它们限制了质子扩散。在本文中，我们使用的计算方法，基于有限差分和有限元方法（FDM和FEM，分别），分析的时空行为的[H+]时，它是局部扰动。我们分析实验数据获得的各种细胞类型（心肌细胞，十二指肠肠上皮细胞，软体动物神经元），其中pH值已成像共聚焦使用细胞内pH敏感染料。我们设计数学算法来生成二维扩散的解决方案，该解决方案适合表观细胞内H+扩散系数DHapp的数据。该模型被用来探讨如何[H+]iis的空间分布的影响膜H+-等效运输和细胞的几何形状。然后，我们开发了一个机制模型，描述时空变化的[H+] i在心肌细胞的H+穿梭在移动的缓冲液和H+锚定在固定的缓冲液。我们还讨论了如何建模可能包括外部碳缓冲的影响。总的来说，我们的计算方法提供了一个框架，为未来的分析生理后果的pHinon均匀性。
Intracellular pH, an important modulator of cell function, is regulated by plasmalemmal proteins that transport H+, or its equivalent, into or out of the cell. The pHiis also stabilised by high-capacity, intrinsic buffering on cytoplasmic proteins, oligopeptides and other solutes, and by the extrinsic CO2/HCO3−(carbonic) buffer. As mobility of these buffers is lower than for the H+ion, they restrict proton diffusion. In this paper we use computational approaches, based on the finite difference and finite element methods (FDM and FEM, respectively), for analysing the spatio-temporal behaviour of [H+] when it is locally perturbed. We analyse experimental data obtained for various cell-types (cardiac myocytes, duodenal enterocytes, molluscan neurons) where pHihas been imaged confocally using intracellular pH-sensitive dyes. We design mathematical algorithms to generate solutions for two-dimensional diffusion that fit data in terms of an apparent intracellular H+diffusion coefficient, DHapp. The models are used to explore how the spatial distribution of [H+]iis affected by membrane H+-equivalent transport and by cell geometry. We then develop a mechanistic model, describing spatio-temporal changes of [H+]iin a cardiac ventricular myocyte in terms of H+-shuttling on mobile buffers and H+-anchoring on fixed buffers. We also discuss how modelling may include the effects of extrinsic carbonic-buffering. Overall, our computational approach provides a framework for future analyses of the physiological consequences of pHinon-uniformity.