Multiple, coordinated Ca2+ -release events underlie the inositol trisphosphate-induced local Ca2+ spikes in mouse...

Ca2+ wave initiation and non-propagating Ca2+ spikes occur as a result of localized Ca2+ release from the more sensitive intracellular Ca2+ stores. Using high spatial and temporal Ca2+ -imaging techniques we have investigated inositol 1,4,5 triphosphate (InsP3)-induced local Ca2+ spiking, which occurs at the site of Ca2+ wave initiation in pancreatic acinar cells. The spatial and temporal organization of a single spike suggested discrete hot spots of Ca2+ release. Further analysis of long trains of Ca2+ spikes demonstrated that these hot spots showed regenerative Ca2+ -release events which were consistently active from spike to spike. Regions adjacent to these hot spots also showed regenerative Ca2+ -release events of similar amplitude but with a much lower frequency of occurrence. We conclude that the InsP3-induced non-propagating Ca2+ spikes can be devolved into smaller components of release. Our results are consistent with a model of coordinated activity of pacemaker hot spots of Ca2+ release that recruit and entrain active Ca2+ -release events from surrounding regions.