A computer model for intracellular pH regulation in Chinese hamster ovary cells

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).