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A Computer Model for Intracellular pH Regulation in Chinese Hamster Ovary Cells
Author(s) -
Wu P.,
Ray N. G.,
Shuler M. L.
Publication year - 1993
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp00022a004
Subject(s) - antiporter , chinese hamster ovary cell , intracellular , steady state (chemistry) , biophysics , chemistry , intracellular ph , biochemistry , biology , membrane , receptor
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 pH i , 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 pH i 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 pH i and the transient response of pH i 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 pH i 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).