Protein kinase C regulates the magnitude and stability of CFTR currents in pancreatic duct cells.
Activation of protein kinase C (PKC) inhibits adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated fluid secretion in rat pancreatic ducts (N. Ashton, R. L. Evans, and B. E. Argent. 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) Cl 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 h) exposure of stimulated duct cells to 100 nM PDBu (a condition that should downregulate PKC) significantly slowed the rate at which CFTR currents run down 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 stability of CFTR currents in pancreatic duct cells.
Winpenny
J P
JP
Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, United Kingdom.
McAlroy
H L
HL
Gray
M A
MA
Argent
B E
BE
D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004553:Electric Conductivity; D008565:Membrane Proteins / Q000502:physiology*; D009281:Naphthalenes; D010183:Pancreatic Ducts / Q000166:cytology / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats
D018118:Chloride Channels; D008565:Membrane Proteins; D009281:Naphthalenes; D011083:Polycyclic Compounds; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C058819:calphostin C