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Lookup NU author(s): Dr Michael Gray,
Dr Catherine O'Reilly,
Dr John Winpenny,
Professor Barry Argent
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Disruption of normal cystic fibrosis transmembrane conductance regulator-(CFTR)-mediated Cl- transport is associated with cystic fibrosis (CF). CFTR is also required for HCO3- transport in many tissues such as the lungs, gastro-intestinal tract, and pancreas, although the exact role CFTR plays is uncertain. Given the importance of CFTR in HCO3- transport by so many CF-affected organ systems, it is perhaps surprising that relatively little is known about the interactions of HCO3- ions with CFTR. We have used patch clamp recordings from native pancreatic duct cells to study HCO3- permeation and interaction with CFTR. Ion selectivity studies shows that CFTR is between 3-5 times more selective for Cl- over HCO3-. In addition, extracellular HCO3- has a novel inhibitory effect on cAMP-stimulated CFTR currents carried by Cl-. The block by HCO3- was rapid, relatively independent of voltage and occurred over the physiological range of HCO3- concentrations. These data show that luminal HCO3- acts as a potent regulator of CFTR, and suggests that inhibition involves an external anion-binding site on the channel. This work has implications not only for elucidating mechanisms of HCO3- transport in epithelia, but also for approaches used to treat CF.
Author(s): Gray MA, O'Reilly C, Winpenny J, Argent B
Publication type: Article
Publication status: Published
Journal: Journal of the Pancreas
Issue: 4 (suppl.)
ISSN (print): 1590-8577
Publisher: E S Burioni Ricerche Bibliografiche
PubMed id: 11875261