Anion interactions with CFTR and consequences for HCO3- transport in secretory epithelia.
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.
Gray
M
M
Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, UK. m.a.gray@ncl.ac.uk
O'Reilly
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C
Winpenny
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Argent
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B
D000818:Animals; D000838:Anions / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000166:cytology
D000838:Anions; D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator