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Functional interactions of HCO3- with cystic fibrosis transmembrane conductance regulator.
JOP 2001; 2(4 Suppl):207-11JOP

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.

Authors+Show Affiliations

Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, United Kingdom. m.a.gray@ncl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

11875261

Citation

Gray, M A., et al. "Functional Interactions of HCO3- With Cystic Fibrosis Transmembrane Conductance Regulator." JOP : Journal of the Pancreas, vol. 2, no. 4 Suppl, 2001, pp. 207-11.
Gray MA, O'Reilly C, Winpenny J, et al. Functional interactions of HCO3- with cystic fibrosis transmembrane conductance regulator. JOP. 2001;2(4 Suppl):207-11.
Gray, M. A., O'Reilly, C., Winpenny, J., & Argent, B. (2001). Functional interactions of HCO3- with cystic fibrosis transmembrane conductance regulator. JOP : Journal of the Pancreas, 2(4 Suppl), pp. 207-11.
Gray MA, et al. Functional Interactions of HCO3- With Cystic Fibrosis Transmembrane Conductance Regulator. JOP. 2001;2(4 Suppl):207-11. PubMed PMID: 11875261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional interactions of HCO3- with cystic fibrosis transmembrane conductance regulator. AU - Gray,M A, AU - O'Reilly,C, AU - Winpenny,J, AU - Argent,B, PY - 2002/3/5/pubmed PY - 2002/4/25/medline PY - 2002/3/5/entrez SP - 207 EP - 11 JF - JOP : Journal of the pancreas JO - JOP VL - 2 IS - 4 Suppl N2 - 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. SN - 1590-8577 UR - https://www.unboundmedicine.com/medline/citation/11875261/Functional_interactions_of_HCO3__with_cystic_fibrosis_transmembrane_conductance_regulator_ L2 - http://www.joplink.net/prev/200107/10.html DB - PRIME DP - Unbound Medicine ER -