scholarly journals Ca2+Activates Cystic Fibrosis Transmembrane Conductance Regulator- and Cl−-dependent HCO Transport in Pancreatic Duct Cells

2002 ◽  
Vol 278 (1) ◽  
pp. 200-207 ◽  
Author(s):  
Wan Namkung ◽  
Jin Ah Lee ◽  
Wooin Ahn ◽  
WonSun Han ◽  
Sung Won Kwon ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Duct ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Duct Cells ◽  
Pancreatic Duct Cells ◽  
Cystic Fibrosis Transmembrane

scholarly journals CFTR Functions as a Bicarbonate Channel in Pancreatic Duct Cells

2009 ◽  
Vol 133 (3) ◽  
pp. 315-326 ◽  
Author(s):  
Hiroshi Ishiguro ◽  
Martin C. Steward ◽  
Satoru Naruse ◽  
Shigeru B.H. Ko ◽  
Hidemi Goto ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Membrane Potential ◽  
Guinea Pig ◽  
Pancreatic Duct ◽  
Apical Membrane ◽  
Transmembrane Conductance Regulator ◽  
Duct Cells ◽  
Pancreatic Duct Cells ◽  
K Concentration ◽  
Significant Pathway

Pancreatic duct epithelium secretes a HCO3−-rich fluid by a mechanism dependent on cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane. However, the exact role of CFTR remains unclear. One possibility is that the HCO3− permeability of CFTR provides a pathway for apical HCO3− efflux during maximal secretion. We have therefore attempted to measure electrodiffusive fluxes of HCO3− 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 (pHi) that occurred in luminally perfused ducts when membrane potential was altered by manipulation of bath K+ concentration. Apical HCO3− fluxes activated by cyclic AMP were independent of Cl− and luminal Na+, and substantially inhibited by the CFTR blocker, CFTRinh-172. Furthermore, comparable HCO3− fluxes observed in ducts isolated from wild-type mice were absent in ducts from cystic fibrosis (ΔF) mice. To estimate the HCO3− permeability of the apical membrane under physiological conditions, guinea pig ducts were luminally perfused with a solution containing 125 mM HCO3− and 24 mM Cl− in the presence of 5% CO2. From the changes in pHi, membrane potential, and buffering capacity, the flux and electrochemical gradient of HCO3− across the apical membrane were determined and used to calculate the HCO3− permeability. Our estimate of ∼0.1 µm sec−1 for the apical HCO3− permeability of guinea pig duct cells under these conditions is close to the value required to account for observed rates of HCO3− secretion. This suggests that CFTR functions as a HCO3− channel in pancreatic duct cells, and that it provides a significant pathway for HCO3− transport across the apical membrane.

CFTR drives Na+- n HCO 3 − cotransport in pancreatic duct cells: a basis for defective HCO 3 − secretion in CF

1999 ◽  
Vol 276 (1) ◽  
pp. C16-C25 ◽  
Author(s):  
Holli Shumaker ◽  
Hassane Amlal ◽  
Raymond Frizzell ◽  
Charles D. Ulrich ◽  
Manoocher Soleimani
Keyword(s):  
Pancreatic Duct ◽  
Basolateral Membrane ◽  
Molecular Evidence ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Duct Cells ◽  
Pancreatic Duct Cells ◽  
Pancreatic Dysfunction ◽  
Cf Transmembrane Conductance Regulator ◽  
Normal Duct

Pancreatic dysfunction in patients with cystic fibrosis (CF) is felt to result primarily from impairment of ductal[Formula: see text] secretion. We provide molecular evidence for the expression of NBC-1, an electrogenic Na+-[Formula: see text]cotransporter (NBC) in cultured human pancreatic duct cells exhibiting physiological features prototypical of CF duct fragments (CFPAC-1 cells) or normal duct fragments [CAPAN-1 cells and CFPAC-1 cells transfected with wild-type CF transmembrane conductance regulator (CFTR)]. We further demonstrate that 1)[Formula: see text] uptake across the basolateral membranes of pancreatic duct cells is mediated via NBC and 2) cAMP potentiates NBC activity through activation of CFTR-mediated Cl− secretion. We propose that the defect in agonist-stimulated ductal[Formula: see text] secretion in patients with CF is predominantly due to decreased NBC-driven[Formula: see text] entry at the basolateral membrane, secondary to the lack of sufficient electrogenic driving force in the absence of functional CFTR.

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