Functional interactions of HCO3 with cystic fibrosis transmembrane conductance regulator

Gray, M. A., O'Reilly, C., Winpenny, J. P. and Argent, B. (2001) Functional interactions of HCO3 with cystic fibrosis transmembrane conductance regulator. JOP - Journal of the Pancreas, 2 (Suppl 4). pp. 207-211.

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Abstract

Disruption of normal cystic fibrosis transmembrane conductance regulator- (CFTR)-mediated Cl(-) transport is associated with cystic fibrosis (CF). CFTR is also required for HCO(3)(-) 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 HCO(3)(-) transport by so many CF-affected organ systems, it is perhaps surprising that relatively little is known about the interactions of HCO(3)(-) ions with CFTR. We have used patch clamp recordings from native pancreatic duct cells to study HCO(3)(-) permeation and interaction with CFTR. Ion selectivity studies shows that CFTR is between 3-5 times more selective for Cl(-) over HCO(3)(-). In addition, extracellular HCO(3)(-) has a novel inhibitory effect on cAMP-stimulated CFTR currents carried by Cl(-). The block by HCO(3)(-) was rapid, relatively independent of voltage and occurred over the physiological range of HCO(3)(-) concentrations. These data show that luminal HCO(3)(-) 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 HCO(3)(-) transport in epithelia, but also for approaches used to treat CF.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: EPrints Services
Date Deposited: 25 Nov 2010 11:09
Last Modified: 20 Jun 2024 10:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/12676
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