Cystic fibrosis transmembrane conductance regulator currents in guinea pig pancreatic duct cells: inhibition by bicarbonate ions

C M O'Reilly, J P Winpenny, B E Argent, M A Gray

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62 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels play an important role in HCO(3)(-) secretion by pancreatic duct cells (PDCs). Our aims were to characterize the CFTR conductance of guinea pig PDCs and to establish whether CFTR is regulated by HCO(3)(-).

METHODS: PDCs were isolated from small intralobular and interlobular ducts, and their Cl(- )conductance was studied using the whole-cell patch clamp technique.

RESULTS: Activation of a typical CFTR conductance by adenosine 3',5'-cyclic monophosphate (cAMP) was observed in 114 of 204 cells (56%). A larger (10-fold), time- and voltage-dependent Cl(-) conductance was activated in 39 of 204 cells (19%). Secretin had a similar effect. Coexpression of both conductances in the same cell was observed, and both conductances had similar anion selectivity and pharmacology. Extracellular HCO(3)(-) caused a dose-dependent inhibition of both currents (K(i), approximately 7 mmol/L), which was independent of intracellular and extracellular pH, and the PCO(2) and CO(3)(2-) content of the bathing solutions.

CONCLUSIONS: Two kinetically distinct Cl(-) conductances are activated by cAMP in guinea pig PDCs. Because these conductances are coexpressed and exhibit similar characteristics (anion selectivity, pharmacology, and HCO(3)(-) inhibition), we conclude that CFTR underlies them both. The inhibition of CFTR by HCO(3)(-) has implications for the current model of pancreatic ductal HCO(3)(-) secretion.

Original languageEnglish
Pages (from-to)1187-96
Number of pages10
JournalGastroenterology
Volume118
Issue number6
DOIs
Publication statusPublished - Jun 2000

Keywords

  • Animals
  • Anions/pharmacokinetics
  • Bicarbonates/metabolism
  • Carbon Dioxide/metabolism
  • Chloride Channels/metabolism
  • Chlorides/metabolism
  • Colforsin/pharmacology
  • Cyclic AMP/pharmacology
  • Cystic Fibrosis/metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator/metabolism
  • Electric Conductivity
  • Electrophysiology
  • Female
  • Guinea Pigs
  • Hydrogen-Ion Concentration
  • Male
  • Membrane Potentials/drug effects
  • Pancreatic Ducts/chemistry
  • Pancreatic Juice/metabolism
  • Secretin/pharmacology
  • Sodium Bicarbonate/pharmacokinetics

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