Cftr and ENaC ion channels mediate NaCl absorption in the mouse submandibular gland

Catalan, Marcelo A.; Nakamoto, Tetsuji; Gonzalez-Begne, Mireya; Camden, Jean M.; Wall, Susan M.; Clarke, Lane L.; Melvin, James E.


Cystic fibrosis is caused by mutations in CFTR, the cystic fibrosis transmembrane conductance regulator gene. Disruption of CFTR-mediated anion conductance results in defective fluid and electrolyte movement in the epithelial cells of organs such as the pancreas, airways and sweat glands, but the function of CFTR in salivary glands is unclear. Salivary gland acinar cells produce an isotonic, plasma-like fluid, which is subsequently modified by the ducts to produce a hypotonic, NaCl-depleted final saliva. In the present study we investigated whether submandibular salivary glands (SMGs) in delta F508 mice (Cftr delta F/delta F) display ion transport defects characteristic of cystic fibrosis in other tissues. Immunolocalization and whole-cell recordings demonstrated that Cftr and the epithelial Na+ (ENaC) channels are co-expressed in the apical membrane of submandibular duct cells, consistent with the significantly higher saliva [NaCl] observed in vivo in Cftr delta F/delta F mice. In contrast, Cftr and ENaC channels were not detected in acinar cells, nor was saliva production affected in Cftr delta F/delta F mice, implying that Cftr contributes little to the fluid secretion process in the mouse SMG. To identify the source of the NaCl absorption defect in Cftr delta F/delta F mice, saliva was collected from ex vivo perfused SMGs. Cftr delta F/delta F glands secreted saliva with significantly increased [NaCl]. Moreover, pharmacological inhibition of either Cftr or ENaC in the ex vivo SMGs mimicked the Cftr delta F/delta F phenotype. In summary, our results demonstrate that NaCl absorption requires and is likely to be mediated by functionally dependent Cftr and ENaC channels localized to the apical membranes of mouse salivary gland duct cells.

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Título según WOS: ID WOS:000274485500016 Not found in local WOS DB
Volumen: 588
Número: 4
Editorial: Wiley
Fecha de publicación: 2010
Página de inicio: 713
Página final: 724


Notas: ISI