Bangel-Ruland N, Sobczak K, Christmann T, Kentrup D, Langhorst H, Kusche-Vihrog K, Weber WM
Characterization of the Epithelial Sodium Channel Delta Subunit in Human Nasal Epithelium. [JOURNAL ARTICLE]
Am J Respir Cell Mol Biol 2009 Jun 11.
The epithelial sodium channel (ENaC) mediates the first step in Na(+) reabsorption in epithelia cells such as kidney, colon, and airways and may consist of four homologous subunits (alpha, beta, gamma, delta). Predominantly, the alpha-subunit is expressed in these epithelia and it usually forms functional channels with the beta- and gamma-subunits. The delta-subunit was first found in human brain and kidney but the expression was also detected in human cell lines of lung, pancreatic and colonic origin. When co-expressed with beta and gamma accessory subunits in heterologous systems the two known isoforms of the delta-ENaC subunit (delta1 and delta2) can build amiloride-sensitive Na(+) channels. In the present study we demonstrate the expression and function of the delta-subunit in human nasal epithelium (HNE). We cloned and sequenced the full-length cDNA of the delta-ENaC subunit and could show that in nasal tissue at least isoform 1 is expressed. Furthermore, we carried out Western blot analyses and compared the cell surface expression of the delta-subunit with the classically expressed alpha-subunit by using immunofluorescence experiments. Thereby, we could show that the quantity of both subunits is almost similar. Additionally, we show the functional expression of the delta-ENaC subunit with measurements in modified Ussing chambers and demonstrate that in HNE a large portion of the Na(+) transport is mediated by the delta-ENaC subunit. Therefore, we suppose that the delta-subunit may possess an important regulatory function and might interact with other ENaC subunits or members of the DEG/ENaC family in the human respiratory epithelium.
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