12] Manipulation and regulation ofcytosolic pH

Abstract

Evaluating how a cell responds to acid or alkali loads is a powerful technique for elucidating the mechanisms, kinetics, and regulation of acid–base transporters responsible for pH i regulation. From intracellular buffering power as well as the rate at which pHi recovers from acute acid or alkali loads, the equivalent acid–base flux responsible for the pHi recovery can be computed. With the results from additional experiments exploiting the specific inhibitors of transporters, it is possible to determine the pH i dependence of these transporters. This is a necessary step for elucidating the physiological control of these transporters. For example, by comparing the pH i dependencies of the Na + /H + exchanger under various conditions, it is possible to determine the effect of second messengers, changes in cell volume, growth factors, and oncogenes on the pH dependence of the Na+/H + exchanger. In the nervous system, regulating the pH dependence of the acid–base transporters that regulate pH i could play a role in neuromodulation and also could be a mechanism for correcting acid–base imbalances that arise during electrical activity.