Intercellular calcium waves in rat pancreatic acini: mechanism of transmission
Yule, D.I.; Stuenkel, E.; Williams, J.A.
American Journal of Physiology 271(4 Pt 1): C1285-C1294
1996
ISSN/ISBN: 0002-9513 PMID: 8897836 Document Number: 462284
Digital-imaging microfluorimetry, together with microinjection of marker/messenger molecules, was utilized to investigate intercellular Ca-2+ signaling in rat pancreatic acinar cells. Stimulation of acini with low concentrations of secretagogues ( lt 100 pM cholecystokinin (CCK), lt 1 mu-M carbachol (CCh)) resulted in asynchronous but coordinated increases in Ca-2+ that appeared to pass in a "wavelike" fashion between cells. In contrast, at higher supermaximal concentrations of agonists ( gt 300 pM CCK, gt 1 mu-M CCh), which induce a large "peak-and-plateau" intracellular Ca-2+ signal, all cells in the acinus appeared to increase Ca-2+ concentration ((Ca-2+)) in synchrony. Microinjection of lissarhodamine, a marker of gap-junctional permeability, into cells previously loaded with fura 2 allowed the simultaneous measurement of gap-junctional coupling and (Ca-2+). Stimulation with supermaximal concentrations of agonists resulted in the attenuation of junctional permeability, whereas, during stimulation with physiological concentrations of agonist, junctional communication remained operable. Injection of inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) into one cell of an acinar cluster resulted in the generation of a Ca-2+ signal in the injected cell and adjacent cells. In contrast, injection of CaCl-2 itself did not result in propagation of the signal. When CaCl-2 was injected into cells that had been previously stimulated with a threshold concentration of CCK, propagation of a signal was observed between cells. On the basis of these data, a model is proposed in which Ca-2+ acts as coagonist with Ins(1,4,5)P-3 to potentiate the Ca-2+-releasing action of Ins(1,4,5)P-3 and, by diffusion of the two molecules through gap junctions, underlies intercellular signaling in acinar cells. Gap-junctional communication may be an important factor in amplifying a threshold signal produced in one cell throughout the acinus, resulting in enhanced stimulated secretion in acinar preparations compared with preparations of isolated cells.