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).
Wu
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School of Chemical Engineering, Cornell University, Ithaca, New York 14853.
Ray
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Shuler
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D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D000641:Ammonia / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002021:Buffers; D016466:CHO Cells / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003198:Computer Simulation; D006224:Cricetinae; D003470:Culture Media; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D007773:Lactates / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid; D008247:Lysosomes / Q000378:metabolism; D008432:Mathematical Computing; D008954:Models, Biological; D017923:Sodium-Hydrogen Exchangers
D000596:Amino Acids; D002021:Buffers; D002352:Carrier Proteins; D003470:Culture Media; D007773:Lactates; D017923:Sodium-Hydrogen Exchangers; D019344:Lactic Acid; D000641:Ammonia; D005947:Glucose