J Korean Med Sci.  2000 Aug;15(Suppl):S12-S15. 10.3346/jkms.2000.15.S.S12.

Anion interactions with CFTR and consequences for HCO3- transport in secretory epithelia

• Gray M
• O'Reilly C
• Winpenny J
• Argent B

• KMID: 1026935
• DOI: http://doi.org/10.3346/jkms.2000.15.S.S12

Abstract

We have been studying CFTR channels in guinea pig pancreatic duct cells and rather surprisingly found that luminal HCO3- had a pronounced inhibitory effect on cAMP-activated CFTR chloride currents. The block produced by HCO3- was rapid, voltage-independent and occurred over a physiological range of extracellular HCO3- concentrations. I- and ClO4- were also found to inhibit CFTR currents, but both were less effective than HCO3-. Although we have not identified how HCO3- is able to block CFTR our data suggests that an external anion-binding site on the channel itself is involved. Overall, our results show that luminal HCO3- acts as a potent inhibitor of CFTR channels (and by inference CFTR-mediated secretion), under normal physiological conditions. These data have implications not only for current models of pancreatic duct cell HCO3- transport, but also for other bicarbonate-secreting tissues, such as the liver, GI tract and lungs.

Keyword

CFTR; Bicarbonate; Epithelia; Patch Clamp

MeSH Terms

Animal
Anions/metabolism
Bicarbonates/metabolism*
Cystic Fibrosis Transmembrane Conductance Regulator/metabolism*
Epithelial Cells/secretion
Epithelial Cells/metabolism*
Pancreatic Ducts/cytology