A Computer Model for Intracellular pH Regulation in Chinese Hamster Ovary Cells

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Abstract
A single‐cell model for Chinese hamster ovary (CHO) cells has been extended to study the regulation of intracellular pH. This model provides for the first time a direct mechanistic linkage between intracellular pH control and cellular metabolism. Among the known mechanisms that regulate and disturb pHi, the Na/H antiport, effect of lactate and ammonia, proton leakage, and external pH have been included in the model. The ability of the model to predict both steady‐state and transient pHi has been tested against experimental studies. The “regular model” that has been used to predict cell growth in suspension and batch cultures can predict the steady‐state pHi and the transient response of pHi to an alkaline load well, but it had to be modified in terms of the maximum activity of the Na/H antiport in order to simulate the transient response of pHi to an acid load. The modification indicates the possibility that a cell could activate the Na/H antiport under acute acid load but return to its basal level of Na/H antiport activity under steady‐state conditions, even when the cell interior is under low‐pH conditions (6.7–7.0).