Intracellular pH and calcium signalling in rat pancreatic acinar cells

Intracellular free Ca2+ signals, which occur in many secretory cell types after the binding of some secretagogues to their membrane receptors, are due to Ca2+ mobilization from internal stores and Ca2+ influx from the extracellular space. There is also growing evidence for a modulatory role of intracellular pH in Ca2+ metabolism. In fact it has been proposed that Ca2+ stores in pancreatic acinar cells may be loaded by Ca2+/H+ exchange. The aim of this paper was to establish the effect of intracellular pH on Ca2+ signalling in pancreatic acinar cells. Application of the proton carrier nigericin impairs Ca2+ mobilization in response to cholecystokinin (CCK-8), and application of membrane-permeant bases or acids inhibits CCK-8-evoked intracellular Ca2+ oscillations. Both nigericin and a cell-permeant weak base release Ca2+ from internal stores. However, cytosolic acidification by removal of extracellular Na+ had no effect on the resting or stimulated cytosolic Ca2+ concentration. After depletion of Ca2+ stores by a maximal concentration of CCK-8, nigericin and ionomycin released a residual Ca2+ pool. Taken together, our results show that in pancreatic acinar cells Ca2+ signals require the existence of subcellular gradients of pH and indicate the presence of acidic pools of Ca2+.