Characterization of two distinct chloride channels in cultured dog
pancreatic duct epithelial cells.
Nguyen, Toan D., Duk-Su Koh[acute]a, Mark W. Moody, Norman R. Fox,
Chris E. Savard, Rahul Kuver, Bertil Hille[acute]a, Sum P. Lee.
Departments of Medicine and Physiology and Biophysics ([acute]a),
University of Washington & Seattle V.A. Medical Center, Seattle,
Washington
APStracts 3:0157G, 1996.
Chloride (Cl-) secretion by pancreatic duct epithelial cells (PDEC)
regulates cellular bicarbonate secretion, an important component of
the exocrine pancreas. In cystic fibrosis, for example, impaired
function of the CFTR Cl- channel results in decreased pancreatic
secretion and secondary pancreatic insufficiency. Studies of ion
transport by PDEC have been hindered by the lack of a practical in
-vitro model. We have successfully cultured non-transformed dog PDEC
on Vitrogen-coated permeable membranes overlying a feeder layer of
myofibroblasts and now report the characterization of Cl- channels in
these cells. Cl- conductance, assessed through efflux of 125I- from
PDEC, was stimulated by agents acting via cAMP or cytosolic Ca2+. The
Cl- conductances activated by cAMP and Ca2+ were distinct since they
were differentially inhibited by DIDS, and to a lesser extent, by
NPPB and DPC. Patch-clamp studies confirmed the presence of Cl-
channels activated by cAMP and Ca2+, with differential inhibition by
DIDS. The presence of CFTR Cl- channels in PDEC was confirmed by
immunoblotting. These cultured PDEC will be an optimal model for
studies of pancreatic duct secretion.
Received 2 October 1995; accepted in final form 6 August 1996.
APS Manuscript Number G423-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996