CFTR Functions as a bicarbonate channel in pancreatic duct cells

Hiroshi Ishiguro, Martin C. Steward, Satoru Naruse, B. H.Ko Shigeru, Hidemi Goto, R. Maynard Case, Takaharu Kondo, Akiko Yamamoto

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Pancreatic duct epithelium secretes a HCO 3-rich f uid by a mechanism dependent on cystic f brosis transmem-brane conductance regulator (CFTR) in the apical membrane. However, the exact role of CFTR remains unclear. One possibility is that the HCO 3- permeability of CFTR provides a pathway for apical HCO 3- eff ux during maxi-mal secretion. We have therefore attempted to measure electrodiffusive f uxes of HCO 3- induced by changes in membrane potential across the apical membrane of interlobular ducts isolated from the guinea pig pancreas. This was done by recording the changes in intracellular pH (pH i ) that occurred in luminally perfused ducts when mem-brane potential was altered by manipulation of bath K + concentration. Apical HCO 3- f uxes activated by cyclic AMP were independent of Cl̃ and luminal Na + , and substantially inhibited by the CFTR blocker, CFTR inh -172. Further-more, comparable HCO3- f uxes observed in ducts isolated from wild-type mice were absent in ducts from cystic f -brosis (ΔF) mice. To estimate the HCO 3- permeability of the apical membrane under physiological conditions, guinea pig ducts were luminally perfused with a solution containing 125 mM HCO 3- and 24 mM Cl̃ in the presence of 5% CO 2 . From the changes in pH i , membrane potential, and buffering capacity, the f ux and electrochemi-cal gradient of HCO 3- across the apical membrane were determined and used to calculate the HCO 3- permeability. Our estimate of M0.1 μ m sec- 1 for the apical HCO 3- permeability of guinea pig duct cells under these conditions is close to the value required to account for observed rates of HCO 3- secretion. This suggests that CFTR functions as a HCO 3- channel in pancreatic duct cells, and that it provides a signif cant pathway for HCO 3 - transport across the apical membrane.

Original languageEnglish
Pages (from-to)315-326
Number of pages12
JournalJournal of General Physiology
Volume133
Issue number3
DOIs
Publication statusPublished - 2009 Mar

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'CFTR Functions as a bicarbonate channel in pancreatic duct cells'. Together they form a unique fingerprint.

  • Cite this

    Ishiguro, H., Steward, M. C., Naruse, S., Shigeru, B. H. K., Goto, H., Case, R. M., Kondo, T., & Yamamoto, A. (2009). CFTR Functions as a bicarbonate channel in pancreatic duct cells. Journal of General Physiology, 133(3), 315-326. https://doi.org/10.1085/jgp.200810122