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Bicarbonate and Chloride Secretion in Calu-3 Human Airway Epithelial Cells
| Content Provider | Scilit |
|---|---|
| Author | Devor, Daniel C. Singh, Ashvani K. Lambert, Linda C. DeLuca, Arthur Frizzell, Raymond A. Bridges, Robert J. |
| Copyright Year | 1999 |
| Abstract | Serous cells are the predominant site of cystic fibrosis transmembrane conductance regulator expression in the airways, and they make a significant contribution to the volume, composition, and consistency of the submucosal gland secretions. We have employed the human airway serous cell line Calu-3 as a model system to investigate the mechanisms of serous cell anion secretion. Forskolin-stimulated Calu-3 cells secrete HCO−3 by a Cl −-independent, serosal Na+-dependent, serosal bumetanide-insensitive, and serosal 4,4′-dinitrostilben-2,2′-disulfonic acid (DNDS)–sensitive, electrogenic mechanism as judged by transepithelial currents, isotopic fluxes, and the results of ion substitution, pharmacology, and pH studies. Similar studies revealed that stimulation of Calu-3 cells with 1-ethyl-2-benzimidazolinone (1-EBIO), an activator of basolateral membrane Ca2+-activated K+ channels, reduced HCO−3 secretion and caused the secretion of Cl − by a bumetanide-sensitive, electrogenic mechanism. Nystatin permeabilization of Calu-3 monolayers demonstrated 1-EBIO activated a charybdotoxin- and clotrimazole- inhibited basolateral membrane K+ current. Patch-clamp studies confirmed the presence of an intermediate conductance inwardly rectified K+ channel with this pharmacological profile. We propose that hyperpolarization of the basolateral membrane voltage elicits a switch from HCO−3 secretion to Cl − secretion because the uptake of HCO−3 across the basolateral membrane is mediated by a 4,4 ′-dinitrostilben-2,2′-disulfonic acid (DNDS)–sensitive Na+:HCO−3 cotransporter. Since the stoichiometry reported for Na +:HCO−3 cotransport is 1:2 or 1:3, hyperpolarization of the basolateral membrane potential by 1-EBIO would inhibit HCO−3 entry and favor the secretion of Cl −. Therefore, differential regulation of the basolateral membrane K+ conductance by secretory agonists could provide a means of stimulating HCO−3 and Cl − secretion. In this context, cystic fibrosis transmembrane conductance regulator could serve as both a HCO−3 and a Cl − channel, mediating the apical membrane exit of either anion depending on basolateral membrane anion entry mechanisms and the driving forces that prevail. If these results with Calu-3 cells accurately reflect the transport properties of native submucosal gland serous cells, then HCO−3 secretion in the human airways warrants greater attention. |
| Related Links | http://jgp.rupress.org/content/113/5/743.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2222914/pdf |
| Ending Page | 760 |
| Page Count | 18 |
| Starting Page | 743 |
| DOI | 10.1085/jgp.113.5.743 |
| Journal | The Journal of general physiology |
| Issue Number | 5 |
| Volume Number | 113 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 1999-05-01 |
| Access Restriction | Open |
| Subject Keyword | Respiratory System Submucosal Glands Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Sodium Bicarbonate Cotransporter Serous Cells Journal: The Journal of general physiology (Vol- 113, Issue- 5) |
| Content Type | Text |
