Regulation of gap junctional communication in CFTR-expressing pancreatic epithelial cells.
Gap junction channels provide a pathway for coordinating multicellular activity. To evaluate the contribution of cell-to-cell communication in the function of epithelial cells, we studied the strength of gap junctional coupling in pancreatic acinar and duct cells exposed to agents known to elevate the intracellular concentration of Ca(2+) or cAMP. In acinar cells, we observed that maximal concentrations of acetylcholine evoked a biphasic increase in cytosolic Ca(2+) mobilization. The second sustained phase, which depends on Ca(2+) influx into the cell, was associated with the rapid closure of gap junction 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 between cells harboring the DeltaF508 mutation of CFTR. An abnormal pattern of gap junctional coupling may contribute to the altered functions of tissues affected in cystic fibrosis.
Chanson
M
M
Laboratory of Clinical Investigation III, Department of Pediatrics, Geneva University Hospital, HUG-PO BOX 14, Micheli-du-Crest, 24, 1211 Geneva 14, Switzerland. marc_chanson@hotmail.com
Suter
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D008297:Male; D010179:Pancreas / Q000166:cytology*; D010183:Pancreatic Ducts / Q000166:cytology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium