Secretin activates Cl- channels in bile duct epithelial cells through a cAMP-dependent mechanism

J. M. McGill, S. Basavappa, T. W. Gettys, J. G. Fitz

Research output: Contribution to journalArticle

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Abstract

Using patch-clamp recording techniques, we assessed the effects of secretin on membrane ion channel activity in isolated rat bile duct epithelial cells. In the whole cell configuration, secretin activated an inward membrane current at -40 mV in 6 of 13 cells, and increased current density from 17 ± 8 to 98 ± 33 pA/pF. Secretin-stimulated currents reversed near the equilibrium potential for Cl- and exhibited a linear current- voltage relationship. In the cell-attached configuration, secretin activated low-conductance channels in 73% (11 of 15) of patches. Similar channels were activated by forskolin, suggesting that adenosine 3',5'-cyclic monophosphate (cAMP) is involved as a second messenger. At the resting membrane potential, channels carried inward membrane current and had a slope conductance of 10 ± 1 pS. In excised patches, addition of purified catalytic subunit of cAMP- dependent protein kinase (protein kinase A) to the cytoplasmic surface activated channels in four of six attempts. With equal Cl- concentrations in bath and pipette, channels had a linear slope conductance of 13 ± 2 pS and currents reversed near 0 mV. Partial substitution of pipette Cl- with gluconate caused a shift in reversal potential in the direction anticipated for a Cl--selective channel (gluconate to Cl- permeability ratio of 0.21 ± 0.05, n = 4). Thus in bile duct epithelial cells, exposure to secretin activates low-conductance, Cl--selective channels, probably through a cAMP- dependent mechanism. This likely contributes to secretin-dependent choleresis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume266
Issue number4 29-4
StatePublished - 1994

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Secretin
Bile Ducts
Epithelial Cells
Cyclic AMP-Dependent Protein Kinases
Ion Channels
Membranes
Second Messenger Systems
Patch-Clamp Techniques
Colforsin
Baths
Cyclic AMP
Membrane Potentials
Permeability
Catalytic Domain

Keywords

  • cystic fibrosis transmembrane conductance regulator protein
  • hepatobiliary secretion
  • patch-clamp recording

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Secretin activates Cl- channels in bile duct epithelial cells through a cAMP-dependent mechanism. / McGill, J. M.; Basavappa, S.; Gettys, T. W.; Fitz, J. G.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 266, No. 4 29-4, 1994.

Research output: Contribution to journalArticle

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