Functional Interactions of HCO3 - with Cystic Fibrosis Transmembrane Conductance Regulator

Mike A Gray, Catherine A O'Reilly, John Winpenny, Barry Argent

Visit for more related articles at

Abstract

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.

open access journals, open access scientific research publisher, open access publisher
Select your language of interest to view the total content in your interested language

Viewing options

Flyer image

Share This Article