Regulation of gap junctional communication in CFTR-expressing pancreatic epithelial cells

Gap junction channels provide a pathway for coordinating multicellular acti vity. To evaluate the contribution of cell-to-cell communication in the fun ction of epithelial cells, we studied the strength of gap junctional coupli ng in pancreatic acinar and duct cells exposed to agents known to elevate t he intracellular concentration of Ca2+ or cAMP. In acinar cells, we observe d that maximal concentrations of acetylcholine evoked a biphasic increase i n cytosolic Ca2+ mobilization. The second sustained phase, which depends on Ca2+ influx into the cell, was associated with the rapid closure of gap ju nction channels. In duct cells, stimulation of CFTR-dependent Cl- currents with cAMP analogs markedly increased gap junctional conductance in pairs of cells. Interestingly, cAMP had no effect on intercellular communication be tween cells harboring the Delta F508 mutation of CFTR. An abnormal pattern of gap junctional coupling may contribute to the altered functions of tissu es affected in cystic fibrosis.