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Functional interactions of HCO3- with cystic fibrosis transmembrane conductance regulator

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.

Publication metadata

Author(s): Gray MA, O'Reilly C, Winpenny J, Argent B

Publication type: Article

Publication status: Published

Journal: Journal of the Pancreas

Year: 2001

Volume: 2

Issue: 4 (suppl.)

Pages: 207-211

ISSN (print): 1590-8577

ISSN (electronic):

Publisher: E S Burioni Ricerche Bibliografiche


PubMed id: 11875261