Premium
Bicarbonate secretion in human small airways
Author(s) -
Shamsuddin A K M,
Quinton Paul M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb687
Subject(s) - cystic fibrosis transmembrane conductance regulator , cystic fibrosis , secretion , bicarbonate , mucin , ussing chamber , chloride channel , chemistry , ion transporter , amiloride , mucus , potentiator , medicine , endocrinology , biophysics , biochemistry , biology , pharmacology , sodium , membrane , ecology , organic chemistry
Cystic Fibrosis (CF) pathology is attributed to a basic defect in epithelial anion transport. The loss of bicarbonate (HCO 3 − ) transport in CF plays a critical role in pathogenesis by interrupting the normal formation and release of mucins in exocrine tissues as in pancreas, liver and intestines in CF, we do not know whether HCO 3 − secretion occurs in normal human native small airways, the most prevalent site of morbidity and mortality in CF. Using our recently developed mini‐Ussing chamber system to determine the properties of HCO 3 − transport in freshly dissected human airways (diameter ≈ 2.0 mm). We assayed HCO 3 − transport by measuring the transepithelial potential, conductance and equivalent short circuit current with bilateral 25 mM NaHCO 3 − plus 125 mM NaGlu in presence of luminal amiloride. Under these conditions since the only major transportable anion present was HCO 3 − , we took the short‐circuit current to be a direct measure of HCO 3 − transport in small airways. Applying selective agonists and/or inhibitors, we show that human native small airways constitutively secrete HCO 3 − , and could be further stimulated agonists mediated by cAMP (adrenergic) and Ca 2+ (purinergic) and respectively inhibited by selective antagonists. These results suggest at least two pathways for HCO 3 − secretion, one dependent on Cystic fibrosis transmembrane conductance regulator (CFTR) and another dependent on a calcium‐activated chloride channel (CaCC), that secrete HCO 3 − into the airway luminal surface liquids, to critically support the discharge of mucins and maintain airway surface liquid pH for optimal defense and hygiene of small airways. By analogy with other organs in CF, failure to secrete HCO 3 − likely results poor mucociliary and pathogen clearance and thus should be seen a new target for therapy in CF and possibly other airway diseases. Support or Funding Information Supported by the Nancy Olmsted Trust, the Cystic Fibrosis Foundation and Cystic Fibrosis Research, Inc.