title: Modelling intracellular H(+) ion diffusion.
abstract: 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.affiliation: Burdon Sanderson Cardiac Science Centre, University Laboratory of Physiology, OX1 3PT, Oxford, UK
authors.forename: Pawel
authors.initials: P
authors.lastname: Swietach
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Zaniboni
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Stewart
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossini
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: Richard D
authors.initials: RD
authors.lastname: Vaughan-Jones
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003198:Computer Simulation; D020895:Enterocytes / Q000737:chemistry / Q000378:metabolism*; D020342:Finite Element Analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D011522:Protons
chemical_list: D011522:Protons