Control of Intracellular pH

Because virtually every biological process is sensitive to changes in pH, acid–base homeostasis is of critical importance to cells and organisms, and has attracted considerable attention. Until relatively recently, acid–base homeostasis, for both clinicians and basic scientists, has been synonymous with pH regulation in the two most easily accessed compartments, blood and cerebrospinal fluid (CSF). The pH in these extracellular compartments (pH o ) is certainly important for organisms. For example, alterations in pH o may affect various extracellular biochemical reactions (e.g., hemostasis, complement fixation) and influence binding of various substances (e.g., hormones, metals, therapeutic agents) to plasma proteins or cell surface receptors. Moreover, certain ion channels as well as transporters that move solutes across cell membranes are sensitive to pH o changes. Nevertheless, the number of processes sensitive to changes of extracellular pH pales in comparison with the myriad processes sensitive to alterations in intracellular pH (pH i ). Thus, pH i homeostasis should be a matter of central importance not only for individual cells, but also for the organism composed of these cells.