Excess divalent cations activate Ca(2+)-mobilizing receptors in pancreatic acinar cells

In single, enzymatically dissociated, rat pancreatic acinar cells, external application of excess divalent cations (Ca2+, Sr2+, Ba2+, Ni2+ and Mg2+ over 50 mM) induced Ca(2+)-dependent current responses monitored with the whole-cell recording technique. Inclusion of either EGTA, heparin or GDP[beta S] in the internal solution or treatment of acinar cells with a phorbol ester abolished the divalent-cation-induced responses. In contrast, internal inositol trisphosphate (InsP3) or GTP[gamma S] potentiated the responses. The results indicate that excess divalent cations activate membrane surface receptors or receptor/effector complexes, thereby inducing InsP3-mediated Ca2+ mobilization. The mechanism may be due to modulation of the receptors by changes in electrical profile through indirect action of divalent cations on membrane surface charges, i.e. neutralization of anionic charges. This proposal was supported by the evidence that the trivalent cation, La3+, and the polyvalent cation, protamine, both at much lower concentrations, could induce Ca(2+)-dependent responses, which were abolished by internal application of heparin, GDP[ beta S] or a high concentration of EGTA or by protein kinase C activation with a phorbol ester.