NH 3 Permeability versus CO 2 Permeability: Insights from Mathematical Modeling

Exposing a cell to a solution containing NH 3 /NH 4 + leads to a rapid NH 3 influx, which causes a rise in intracellular pH (pH i ) and a transient decrease in surface pH (pH S ). Conversely, exposing a cell to a solution containing CO 2 /HCO 3 − leads to a rapid CO 2 influx, which causes a fall in pH i and a transient increase in pH S . In our laboratory we use the maximal change in the height of the pH S transient (ΔpH S ) as a semiquantitative index of membrane permeability to NH 3 ( P M,NH3 ) or to CO 2 ( P M,CO2 ). As a first step in extracting absolute membrane permeability from pH S measurements, in 2012 we developed a reaction‐diffusion mathematical model of CO 2 influx to investigate the dependence of ΔpH S predicted by the model on P M,CO2 values (Somersalo et al, J Theor Biol , 2012). To account for physiological data on gas channels, the model predicts that,contrary to widespread assumptions, the membrane must offer considerable resistance to the movement of CO 2 . Here, we investigate the dependence of ΔpH S versus P M,NH3 with a reaction‐diffusion mathematical model of NH 3 influx into a spherical cell. The model is an extension of the model of Somersalo et al, in which now we include the NH 3 /NH 4 + buffer equilibrium and passive transmembrane flux of NH 3 . After having checked that the model correctly predicts the transient changes in pH i and pH S that one would expect as NH 3 enters a cell, we performed simulations in which we systematically decreased P M,NH3 from that corresponding to a thin film of water. By comparing the dependence of ΔpH S versus a range of P M,NH3 (present study) with the dependence of ΔpH S versus P M,CO2 (Somersalo et al), we conclude that, contrary to the Overton's prediction (which considers only solubility in the membrane), the background P M,NH3 (in absence of gas channels) is far higher than the background P M,CO2 .