Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia.
AUTOR(ES)
Anderson, M P
RESUMO
The genetic disease cystic fibrosis (CF) causes decreased Cl- transport in several epithelia. cAMP-dependent regulation of apical membrane Cl- channels is defective in CF airway epithelia; as a result, CF epithelia fail to secrete Cl-. In contrast, Ca(2+)-stimulated Cl- secretion is intact in CF airway epithelia and thus has the potential to bypass the CF Cl- secretory defect. For a Cl- channel to govern Cl- secretion, it must be located in the apical membrane. To specifically investigate apical membrane Cl- channels, we studied cells grown on permeable filter supports and measured Cl- currents across the apical membrane. We found that Ca2+ and cAMP activate different Cl- channels in the apical membrane. (i) Ca(2+)-activated Cl- channels were present in the apical membrane of airway but not in intestinal epithelia. (ii) cAMP- but not Ca(2+)-activated Cl- channels were defective in CF airway epithelia. (iii) Ca(2+)- but not cAMP-activated Cl- channels were blocked by 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate. (iv) Ca(2+)- and cAMP-activated apical channels had different anion permeabilities. (v) An increase in both second messengers produced an additive increase in Cl- current. These results also explain the puzzling observation that Ca(2+)-stimulated Cl- secretion is defective in CF intestine: the Ca(2+)-activated Cl- channels that could circumvent the Cl- secretory defect in CF airway are missing from the apical membrane of intestinal epithelia.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=52010Documentos Relacionados
- cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia.
- Fatty acids inhibit apical membrane chloride channels in airway epithelia.
- GTP-binding proteins inhibit cAMP activation of chloride channels in cystic fibrosis airway epithelial cells.
- Localization of cystic fibrosis transmembrane conductance regulator in chloride secretory epithelia.
- Chloride secretory response of cystic fibrosis human airway epithelia. Preservation of calcium but not protein kinase C- and A-dependent mechanisms.
