Protein kinase c regulates the magnitude and stability of cftr currents
in pancreatic duct cells.
Winpenny, J. P., H. L. McAlroy, M. A. Gray, and B. E. Argent.
Department of Physiological Sciences, University Medical School,
Framlington Place, Newcastle upon Tyne NE2 4HH, U.K.
APStracts 2:0009C, 1995.
Activation of protein kinase C (PKC) inhibits cAMP-stimulated fluid secretion
in rat pancreatic ducts (Ashton, N. et al., J. Physiol. Lond. 452: 99P, 1992).
Using the patch clamp technique we have investigated whether this inhibition
of fluid secretion results from an effect of PKC on cystic fibrosis
transmembrane conductance regulator (CFTR) chloride channels. Exposure to 100
nM 4[beta]-phorbol 12,13-dibutyrate (PDBu) had no effect on CFTR current
density in unstimulated duct cells, but caused a 31% increase in the magnitude
of CFTR currents recorded from cells stimulated with cAMP. Furthermore,
prolonged (2 - 4 hrs) exposure of stimulated duct cells to 100 nM-PDBu (a
condition which should down-regulate PKC) significantly slowed the rate at
which CFTR currents rundown after establishing a whole-cell recording. A
similar effect was observed with Calphostin C (500 nM), a specific inhibitor
of PKC. Thus although inhibition of ductal fluid secretion by PDBu is
unlikely to be explained by an effect on CFTR, modulation of PKC activity can
affect both the magnitude and the stability of CFTR currents in pancreatic
duct cells.
Received 8 August 1994; accepted in final form 27 October 1994
APS Manuscript Number C0469-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.