Inositol triphosphate produces different patterns of cytoplasmic Ca2+ spiking depending on its concentration

Abstract

In single mouse pancreatic acinar cells the effects of intracellular infusion of inositol 1,4,5-trisphosphate (InsP₃) or the non-metabolizable InsP₃ analogue inositol 1,4,5-triphosphorothioate (InsPS₃) have been investigated using a wide range of concentrations. Different types of cytosolic Ca²⁺ fluctuation patterns (monitored as Ca²⁺-dependent Cl⁻ current in patch-clamp whole-cell recording experiments) could be generated by InsP₃ or InsPS₃, dependent on concentration, resembling those previously shown to be evoked by varying degrees or receptor activation in these cells. Low InsPS₃ concentrations evoked repetitive local Ca²⁺ spikes whereas at relatively high concentrations repetitive Ca²⁺ waves were produced. In the presence of intracellular citrate a much lower messenger level was sufficient to generate waves. The InsP₃ concentration determines whether the cytosolic Ca²⁺ signals are local or global.