Mechanisms of bicarbonate secretion: lessons from the airways

• Published in: Cold Spring Harbor perspectives in medicine Vol. 2; no. 8; p. a015016
• Main Author: Bridges, Robert J
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.08.2012
• Subjects: Benzimidazoles - pharmacology; Bicarbonates - antagonists & inhibitors; Bicarbonates - metabolism; Bronchi - cytology; Bronchi - metabolism; Calcium - metabolism; Calcium Channel Agonists - pharmacology; Calcium Channels - drug effects; Cell Line; Colforsin - pharmacology; Cyclic AMP - antagonists & inhibitors; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - physiology; Electric Impedance; Humans; Intermediate-Conductance Calcium-Activated Potassium Channels - drug effects; Intermediate-Conductance Calcium-Activated Potassium Channels - physiology; Membrane Potentials - drug effects; Microelectrodes; Serous Membrane - drug effects
• ISSN: 2157-1422; 2472-5412
• DOI: 10.1101/cshperspect.a015016

Early studies showed that airway cells secrete HCO(3)(-) in response to cAMP-mediated agonists and HCO(3)(-) secretion was impaired in cystic fibrosis (CF). Studies with Calu-3 cells, an airway serous model with high expression of CFTR, also show the secretion of HCO(3)(-) when cells are stimulated with cAMP-mediated agonists. Activation of basolateral membrane hIK-1 K(+) channels inhibits HCO(3)(-) secretion and stimulates Cl(-) secretion. CFTR mediates the exit of both HCO(3)(-) and Cl(-) across the apical membrane. Entry of HCO(3)(-) on a basolateral membrane NBC or Cl(-) on the NKCC determines which anion is secreted. Switching between these two secreted anions is determined by the activity of hIK-1 K(+) channels.