A role for two-pore K⺠channels in modulating Na⺠absorption and Cl⻠secretion in normal human bronchial epithelial cells.
Am J Physiol Lung Cell Mol Physiol
; 302(1): L4-L12, 2012 Jan 01.
Article
de En
| MEDLINE
| ID: mdl-21964404
ABSTRACT
Mucociliary clearance is the primary innate physical defense mechanism against inhaled pathogens and toxins. Vectorial ion transport, primarily sodium absorption and anion secretion, by airway epithelial cells supports mucociliary clearance. This is evidenced by diseases of abnormal ion transport such as cystic fibrosis and pseudohypoaldosteronism that are characterized by changes in mucociliary clearance. Sodium absorption and chloride secretion in human bronchial epithelial cells depend on potassium channel activity, which creates a favorable electrochemical gradient for both by hyperpolarizing the apical plasma membrane. Although the role of basolateral membrane potassium channels is firmly established and extensively studied, a role for apical membrane potassium channels has also been described. Here, we demonstrate that bupivacaine and quinidine, blockers of four-transmembrane domain, two-pore potassium (K2P) channels, inhibit both amiloride-sensitive sodium absorption and forskolin-stimulated anion secretion in polarized, normal human bronchial epithelial cells at lower concentrations when applied to the mucosal surface than when applied to the serosal surface. Transcripts from four genes, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2), and KCNK6 (TWIK-2), encoding K2P channels were identified by RT-PCR. Protein expression at the apical membrane was confirmed by immunofluorescence. Our data provide further evidence that potassium channels, in particular K2P channels, are expressed and functional in the apical membrane of airway epithelial cells where they may be targets for therapeutic manipulation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Sodium
/
Chlorures
/
Polarité de la cellule
/
Muqueuse respiratoire
/
Canaux potassiques à pores à domaines en tandem
Limites:
Humans
Langue:
En
Journal:
Am J Physiol Lung Cell Mol Physiol
Sujet du journal:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Année:
2012
Type de document:
Article