Pacing intracellular Ca²⁺ signals in exocrine acinar cells

An increase in intracellular [Ca²⁺] in exocrine acinar cells resident in the salivary glands or pancreas is a fundamental event that drives fluid secretion and exocytosis of proteins. Stimulation with secretagogues initiates Ca²⁺ signals with precise spatiotemporal properties thought to be important for driving physiological output. Both in vitro, in acutely isolated acini, and in vivo, in animals expressing genetically encoded indicators, individual cells appear specialized to initiate Ca²⁺ signals upon stimulation. Furthermore, these signals appear to spread to neighbouring cells. These properties are present in the absence of a conventional pacemaker mechanism dependent on the cyclical activation of Ca²⁺-dependent or Ca²⁺-conducting plasma membrane ion channels. In this article, we propose a model for 'pacing' intracellular Ca²⁺ signals in acinar cells based on the enhanced sensitivity of a subpopulation of individual cells and the intercellular diffusion through gap junctions of inositol 1,4,5-trisphosphate and Ca²⁺ to neighbouring cells.