Differential role of cation and anion exchange in lymphocyte pH regulation

In lymphocytes, the Na+/H+ antiport is well suited to function in cytoplasmic pH (pHi) regulation. It is activated by departures from the physiological pHi and is thermodynamically poised to compensate for the tendency of the cells to become acidic. The driving force for H+ (equivalent) efflux is indirectly provided by the Na+ pump. Lymphocytes also possess a cation-independent anion (Cl-/HCO3-) exchange system, which, under the appropriate conditions, tends to restore pHi after an alkali load. Unlike the cation antiport, the source of energy driving the anion exchanger, i.e. the factors that determine the transmembrane Cl- distribution, is not well understood. The contribution of conductive pathways appears to be minimal, resulting in a marked difference between the membrane potential and ECl-. Instead, ECl- is very similar to EH+. Moreover, changes in the distribution of Cl- lead to alterations in the transmembrane delta pH and vice versa, suggesting a relationship between these parameters. Evidence is presented which suggests that the transmembrane distribution of HCO3-, dictated by delta pH, is a major determinant of the intracellular Cl- concentration, a process mediated by the anion exchanger. Thus, if Cl- is driven by the gradient of HCO3-, the cation-independent anion exchanger cannot play an active role in determining pHi. Instead, Cl-/HCO3- exchange may simply stabilize pHi by increasing the dynamic buffering power of the cells. Cation-independent Cl-/HCO3- exchange could be involved in pHi regulation only if coupled to a separate mechanism of intracellular Cl- accumulation, such as Na+-K+-2Cl- co-transport or an inward Cl- pump, which have not been detected in lymphoid cells.(ABSTRACT TRUNCATED AT 250 WORDS)