title: Evidence from mathematical modeling that carbonic anhydrase II and IV enhance CO2 fluxes across Xenopus oocyte plasma membranes.
abstract: Exposing an oocyte to CO2/HCO3 (-) causes intracellular pH (pHi) to decline and extracellular-surface pH (pHS) to rise to a peak and decay. The two companion papers showed that oocytes injected with cytosolic carbonic anhydrase II (CA II) or expressing surface CA IV exhibit increased maximal rate of pHi change (dpHi/dt)max, increased maximal pHS changes (ΔpHS), and decreased time constants for pHi decline and pHS decay. Here we investigate these results using refinements of an earlier mathematical model of CO2 influx into a spherical cell. Refinements include 1) reduced cytosolic water content, 2) reduced cytosolic diffusion constants, 3) refined CA II activity, 4) layer of intracellular vesicles, 5) reduced membrane CO2 permeability, 6) microvilli, 7) refined CA IV activity, 8) a vitelline membrane, and 9) a new simulation protocol for delivering and removing the bulk extracellular CO2/HCO3 (-) solution. We show how these features affect the simulated pHi and pHS transients and use the refined model with the experimental data for 1.5% CO2/10 mM HCO3 (-) (pHo = 7.5) to find parameter values that approximate ΔpHS, the time to peak pHS, the time delay to the start of the pHi change, (dpHi/dt)max, and the change in steady-state pHi. We validate the revised model against data collected as we vary levels of CO2/HCO3 (-) or of extracellular HEPES buffer. The model confirms the hypothesis that CA II and CA IV enhance transmembrane CO2 fluxes by maximizing CO2 gradients across the plasma membrane, and it predicts that the pH effects of simultaneously implementing intracellular and extracellular-surface CA are supra-additive.
authors: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio; rossana.occhipinti@case.edu.
authors: Rossana
authors: R
authors: Occhipinti
authors: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio; Department of Physiology and Biophysics, University of Sao Paulo, Institute of Biomedical Sciences, Sao Paulo, Brazil.
authors: Raif
authors: R
authors: Musa-Aziz
authors: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio; and.
authors: Walter F
authors: WF
authors: Boron
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D002245:Carbon Dioxide / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D030741:Carbonic Anhydrase IV / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D014817:Vitelline Membrane / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide; D024402:Carbonic Anhydrase II; D030741:Carbonic Anhydrase IV; C548247:CA4 protein, human
keywords: buffers; competing equilibria; intracellular pH; reaction-diffusion; surface pH; tortuosity factors