Intracellular pH and calcium signalling in rat pancreatic acinar cells

Abstract

 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⁺.