Cystic fibrosis transmembrane conductance regulator regulates luminal Cl-/HCO3/- exchange in mouse submandibular and pancreatic ducts

Min Goo Lee, Joo Young Choi, Xiang Luo, Elizabeth Strickland, Philip J. Thomas, Shmuel Muallem

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150 Citations (Scopus)

Abstract

We have demonstrated previously the regulation of Cl-/HCO3/- exchange activity by the cystic fibrosis transmembrane conductance regulator (CFTR) in model systems of cells stably or transiently transfected with CFTR (Lee, M. G., Wigley, W. C., Zeng, W., Noel, L. E., Marino, C. R., Thomas, P. J., and Muallem, S. (1999) J. Biol. Chem. 274, 3414-3421). In the present work we examine the significance of this regulation in cells naturally expressing CFTR. These include the human colonic T84 cell line and the mouse submandibular gland and pancreatic ducts, tissues that express high levels of CFTR in the luminal membrane. As in heterologous expression systems, stimulation of T84 cells with forskolin increased the Cl-/HCO3/- exchange activity independently of CFTR Cl- channel activity. Freshly isolated submandibular gland ducts from wild type mice showed variable Cl-/HCO3/- exchange activity. Measurement of [Cl-](i) revealed that this was largely the result of variable steady-state [Cl-](i). Membrane depolarization with 5 nM Ba2+ or 100 nM K+ increased and stabilized [Cl-](i). Under depolarized conditions wild type and ΔF/ΔF mice had comparable basal Cl-/HCO3/- exchange activity. Notably, stimulation with forskolin increased Cl- /HCO3/- exchange activity in submandibular gland ducts from wild type but not ΔF/ΔF mice. Microperfusion of the main pancreatic duct showed Cl- /HCO3/- exchange activity in both the basolateral and luminal membranes. Stimulation of ducts from wild type animals with forskolin had no effect on basolateral but markedly stimulated luminal C1-/HCO3/- exchange activity. By contrast, forskolin had no effect on either basolateral or luminal Cl- /HCO3/- exchange activity of ducts from ΔF/ΔF animals. We conclude that CFTR regulates luminal Cl-/HCO3/- exchange activity in CFTR-expressing cells, and we discuss the possible physiological significance of these findings regarding cystic fibrosis.

Original languageEnglish (US)
Pages (from-to)14670-14677
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number21
DOIs
StatePublished - May 21 1999

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Cystic Fibrosis Transmembrane Conductance Regulator
Pancreatic Ducts
Ducts
Colforsin
Submandibular Gland
Membranes
Animals
Wild Animals
Depolarization
Cystic Fibrosis
Cells
Tissue
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cystic fibrosis transmembrane conductance regulator regulates luminal Cl-/HCO3/- exchange in mouse submandibular and pancreatic ducts. / Lee, Min Goo; Choi, Joo Young; Luo, Xiang; Strickland, Elizabeth; Thomas, Philip J.; Muallem, Shmuel.

In: Journal of Biological Chemistry, Vol. 274, No. 21, 21.05.1999, p. 14670-14677.

Research output: Contribution to journalArticle

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AU - Strickland, Elizabeth

AU - Thomas, Philip J.

AU - Muallem, Shmuel

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