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Cftr and ENaC ion channels mediate NaCl absorption in the mouse submandibular gland
Author(s) -
Catalán Marcelo A.,
Nakamoto Tetsuji,
GonzalezBegne Mireya,
Camden Jean M.,
Wall Susan M.,
Clarke Lane L.,
Melvin James E.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.183541
Subject(s) - epithelial sodium channel , cystic fibrosis , cystic fibrosis transmembrane conductance regulator , submandibular gland , endocrinology , saliva , medicine , chemistry , ductal cells , transepithelial potential difference , exocrine gland , salivary gland , secretion , epithelium , ion transporter , biology , sodium , pancreas , pathology , biochemistry , membrane , organic chemistry
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 ΔF508 mice ( Cftr ΔF/ΔF ) 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 ΔF/ΔF mice. In contrast, Cftr and ENaC channels were not detected in acinar cells, nor was saliva production affected in Cftr ΔF/ΔF 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 ΔF/ΔF mice, saliva was collected from ex vivo perfused SMGs. Cftr ΔF/ΔF glands secreted saliva with significantly increased [NaCl]. Moreover, pharmacological inhibition of either Cftr or ENaC in the ex vivo SMGs mimicked the Cftr ΔF/ΔF 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.