Subcellular distribution of Ca2+ release channels underlying Ca2+ waves and oscillations in exocrine pancreas

Agonists trigger Ca2+ waves and oscillations in exocrine gland cells. Our confocal Ca2+ imaging revealed three distinct phases during the Ca2+ waves in the rat pancreatic acinar cell. Rises in Ca2+ concentration were initiated at a small trigger zone, or T zone, in the granular area; then, Ca2+ waves rapidly spread within the area and, at high agonist concentrations, propagated slowly toward the basal pole. Injection of inositol 1,4,5-trisphosphate (IP3) or Ca2+ from patch pipettes demonstrated the presence of high sensitivity IP3 receptors at the T zone, Ca2+-induced Ca2+ release channels in the granular area, and low sensitivity IP3 receptors in the basal area. The IP3 receptors at the T zone appeared to generate autonomous Ca2+ spikes and to initiate patterned Ca2+ oscillations. Thus, heterogeneous cytosolic localization of Ca2+ release channels plays a key role in Ca2+ waves and oscillations.