Modelling intracellular H(+) ion diffusion.

Journal article

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 pH(i) is also stabilised by high-capacity, intrinsic buffering on cytoplasmic proteins, oligopeptides and other solutes, and by the extrinsic CO(2)/HCO(3)(-) (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 pH(i) has 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, D(H)(app). The models are used to explore how the spatial distribution of [H(+)](i) is affected by membrane H(+)-equivalent transport and by cell geometry. We then develop a mechanistic model, describing spatio-temporal changes of [H(+)](i) in 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 pH(i) non-uniformity.

Authors: Swietach, P; Zaniboni, M; Stewart, A; Rossini, A; Spitzer, K

• Publication status: Published
• Journal: Progress in biophysics and molecular biology
• Volume: 83
• Issue: 2
• Pages: 69-100
• Publication date: 2003-10-01
• DOI: 10.1016/s0079-6107(03)00027-0
• EISSN: 1873-1732
• ISSN: 0079-6107
• Language: English
• Keywords: Finite Element Analysis; Protons; Enterocytes; Myocytes, Cardiac; Models, Biological; Computer Simulation; Animals; Humans; Biological Transport; Intracellular Space; Hydrogen-Ion Concentration; Neurons