Mathematical modeling of the effects of ammonium ion on the intracellular pH of hybridoma cells

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Abstract
A mathematical model for the effects of NH4Cl addition to the growth medium on hybridoma cell intracellular pH (pHi) is presented which includes a detailed description of the properties of the Na+/H+ exchanger. The model is used to calculate the steady‐state value of pHi as a function of the extracellular NH4Cl concentration, employing parameter values taken from the literature except for the cell permeability to NH4+ This parameter value, estimated to be 3.5 × 10−7 cm/s, is obtained by fitting simulation results to experimental data obtained previously for the steady‐state value of pHi in the presence of 10mM NH4Cl. The model simulates well the major features of previously observed experimental pHi changes following NH4Cl addition: the transient characteristics, dependence on the NH4Cl concentration, and lack of dependence on the external pH value. The effect of parameter variations on model results is also investigated in additional simulations. The general modeling framework employed here should be useful for other types of mammalian cells.