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

Lookup NU author(s): Dr Catherine O'Reilly, Dr John Winpenny, Professor Barry Argent, Dr Michael GrayORCiD

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Abstract

Background and Aims: Cystic fibrosis transmembrane conductance regulator (CFTR) CI- channels play an important role in HCO3- 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 HCO3-. 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 HCO3- caused a dose-dependent inhibition of both currents (K(j), ~7 mmol/L), which was independent of intracellular and extracellular pH, and the PCO2 and CO32- content of the bathing solutions. Conclusions: Two kinetically distinct Cl- conductances are activated by cAMP in7 guinea pig PDCs. Because these conductances are coexpressed and exhibit similar characteristics (anion selectivity, pharmacology, and HCO3- inhibition), we conclude that CFTR underlies them both. The inhibition of CFTR by HCO3- has implications for the current model of pancreatic ductal HCO3- secretion.

Publication metadata

Author(s): Winpenny JP; Gray MA; Argent BE; O'Reilly CM

Publication type: Article

Publication status: Published

Journal: Gastroenterology

Year: 2000

Volume: 118

Issue: 6

Pages: 1187-1196

ISSN (print): 0016-5085

ISSN (electronic): 1528-0012

Publisher: W. B. Saunders Co.

URL: http://dx.doi.org/10.1016/S0016-5085(00)70372-6

DOI: 10.1016/S0016-5085(00)70372-6

PubMed id: 10833494

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