Pancreatic calcium waves and secretion.

Abstract

Pancreatic acinar cells display stereotypic Ca2+ waves resulting from Ca2+ release from internal stores during stimulation. The Ca2+ waves are initiated at the luminal pole, and, at high agonist concentrations, spread towards the basal pole. Two key mechanisms behind the generation of Ca2+ waves have been identified. First, the Ca2+ waves are composite, mediated by three distinct Ca2+ release mechanisms with a polarized distribution: high-sensitivity inositol 1,4,5-trisphosphate (InsP3) receptors at a small trigger zone (T zone) in the secretory granule area, Ca(2+)-induced Ca2+ release channels in the granular area and low-sensitivity InsP3 receptors in the basal area. Second, InsP3 can readily diffuse in the cytosol, whereas rises in cytosolic Ca2+ concentration ([Ca2+]i) can be confined through strong buffering and sequestration of Ca2+. InsP3 is thus used as a long-range messenger to transmit agonist signals to the T zone, and [Ca2+]i rises at the T zone are used as a local switch. These mechanisms enable preferential activation of the T zone, irrespective of localization of stimuli and agonist receptors. The secretion of enzymes and fluid is a direct consequence of [Ca2+]i rises at the T zone. The Ca2+ waves and oscillations probably boost the T zone functions.