A Theoretical Analysis of Intracellular Oxygen Diffusion

Oxygen diffusion rates within cells may be heterogeneous, with more rapid diffusion occurring along intracellular pathways of high oxygen solubility, such as mitochondria. Recent experimental data indicate that tissue oxygen permeability rises sharply in a temperature range associated with phase transitions in lipid membranes suggesting that membranes may function as oxygen "pathway". The experimental data have been analyzed using theoretical models of diffusion in two-phase media. By assuming muscles to be composed entirely of aqueous cytosol and lipids, cytosolic permeability was determined as a function of temperature by matching the experimental values of tissue permeability with those of model predictions usingin vitrovalues of lipid permeability. Cytosolic permeability ranged from 50% of water permeability (low temperature) to 90% of water permeability (high temperature) and its temperature dependence was distinctly different from that of water. An upper bound for cytosolic permeability was calculated using a physiologic value for protein volume fraction, and lipid permeability was obtained using this cytosolic permeability. A model with a parallel arrangement of lipid and cytosol yielded a value of lipid permeability that was 71% higher than thein vitrovalue. Intracellular permeabilities calculated from tissue permeability values were found to be inconsistent with experimentally reported values for rat cardiac myocytes. Comparison of three different muscles exhibited the same trend of higher permeability with higher lipid content. It is concluded that both lipid and cytosol permeabilities and, hence, tissue permeabilities are different among different muscles and one should exercise caution when data from one muscle is used to calculate or extrapolate values in other muscles. It is conceivable that muscles with very high mitochondrial content, such as diaphragm and cardiac muscles may exhibit an oxygen permeability which is significantly higher than commonly accepted values. These results warrant additional measurements of tissue oxygen permeability at 37 °C, especially for oxidative muscles with high lipid content.