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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 118; no. 6; p. 1187
• Main Authors: O'Reilly, C M, Winpenny, J P, Argent, B E, Gray, M A
• Format: Journal Article
• Language: English
• Published: United States 01.06.2000
• Subjects: 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; Membrane Potentials - physiology; Pancreatic Ducts - chemistry; Pancreatic Ducts - metabolism; Pancreatic Juice - metabolism; Secretin - pharmacology; Sodium Bicarbonate - pharmacokinetics
• ISSN: 0016-5085
• DOI: 10.1016/s0016-5085(00)70372-6

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