Experimental Generation and Computational Modeling of Intracellular pH Gradients in Cardiac Myocytes
| Autor: | Chae Hun Leem, Pawel Swietach, Kenneth W. Spitzer, R D Vaughan-Jones |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Cytoplasm Heart Ventricles Intracellular pH Diffusion Guinea Pigs Analytical chemistry Biophysics Acetates Buffers Models Biological Ion 03 medical and health sciences Ammonia chemistry.chemical_compound Acetic acid Sarcolemma 0302 clinical medicine Animals Myocytes Cardiac Cell Size 030304 developmental biology HEPES 0303 health sciences Microscopy Confocal Models Statistical Chemiosmosis Models Cardiovascular Proton-Motive Force Carbon Dioxide Hydrogen-Ion Concentration Fick's laws of diffusion Carbon Perfusion Quaternary Ammonium Compounds Microscopy Fluorescence chemistry Cell Biophysics Protons 030217 neurology & neurosurgery |
| Zdroj: | Biophysical Journal. 88(4):3018-3037 |
| ISSN: | 0006-3495 |
| DOI: | 10.1529/biophysj.104.051391 |
| Popis: | It is often assumed that pHi is spatially uniform within cells. A double-barreled microperfusion system was used to apply solutions of weak acid (acetic acid, CO2) or base (ammonia) to localized regions of an isolated ventricular myocyte (guinea pig). A stable, longitudinal pHi gradient (up to 1 pHi unit) was observed (using confocal imaging of SNARF-1 fluorescence). Changing the fractional exposure of the cell to weak acid/base altered the gradient, as did changing the concentration and type of weak acid/base applied. A diffusion-reaction computational model accurately simulated this behavior of pHi. The model assumes that \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{H}}_{{\mathrm{i}}}^{+}\end{equation*}\end{document} movement occurs via diffusive shuttling on mobile buffers, with little free H+ diffusion. The average diffusion constant for mobile buffer was estimated as 33 × 10−7 cm2/s, consistent with an apparent \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{H}}_{{\mathrm{i}}}^{+}\end{equation*}\end{document} diffusion coefficient, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}D_{{\mathrm{H}}}^{{\mathrm{app}}}\end{equation*}\end{document}, of 14.4 × 10−7 cm2/s (at pHi 7.07), a value two orders of magnitude lower than for H+ ions in water but similar to that estimated recently from local acid injection via a cell-attached glass micropipette. We conclude that, because \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{H}}_{{\mathrm{i}}}^{+}\end{equation*}\end{document} mobility is so low, an extracellular concentration gradient of permeant weak acid readily induces pHi nonuniformity. Similar concentration gradients for weak acid (e.g., CO2) occur across border zones during regional myocardial ischemia, raising the possibility of steep pHi gradients within the heart under some pathophysiological conditions. |
| Databáze: | OpenAIRE |
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