Abstract
Introduction: The concentration-sensitive Na+ channel (NaC), a member of the family of voltage-dependent Na+ channels, opens in response to increased Na+ concentration in the extracellular fluid ([Na+]o). Although the expression of NaC in alveolar epithelial type II (AT II) cells has been reported, the physiological role of NaC in lung tissue has not yet been established. Various ion channels in the alveolar epithelium are involved in maintaining the alveolar fluid balance; therefore, we hypothesized that NaC-mediated Na+ transport contributes to the clearance of Na+ from the alveolar fluid. In this study, we examined NaC distribution in mouse lung tissue and the [Na+]o-dependent influx of Na+ into mouse alveolar epithelium.
Methods: We used immunohistochemistry and immunofluorescence to study mouse lung tissue using antibodies against NaC and other ion transport proteins. In situ hybridization was performed using a digoxigenin-labeled antisense probe for NaC mRNA. Na+ dynamics in mouse alveolar epithelium were analyzed using sodium-binding benzofuran isophthalate and an image analyzer Argus-50.
Results: The alveolar epithelial type I (AT I) cells showed positive staining with anti-NaC antibodies. Similarly, NaC mRNA signals were detected in the AT I cells by in situ hybridization. Confocal laser scanning microscopy showed the presence of NaC in the cell membrane of the AT I cells. NaC was partially colocalized with γ epithelial sodium channels (ENaC). Results of image analysis showed that Na+ influx into alveolar epithelium was dependent on elevation of [Na+]o.
Conclusions: These findings suggest that NaC, expressed in AT I cells, is involved in Na+ transport in the alveolar epithelium.
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