Characterization of the epithelial sodium channel delta-subunit in human nasal epithelium.
The epithelial sodium channel (ENaC) mediates the first step in Na+ reabsorption in epithelial 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 were able to show that in nasal tissue at least isoform 1 is expressed. Furthermore, we performed 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. In addition, 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.
Bangel-Ruland
Nadine
N
Institute of Animal Physiology, University of Muenster, Hindenburgplatz 55, 48143 Muenster, Germany. bangel@uni-muenster.de
Sobczak
Katja
K
Christmann
Tina
T
Kentrup
Dominik
D
Langhorst
Hanna
H
Kusche-Vihrog
Kristina
K
Weber
Wolf-Michael
WM
D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D053503:Epithelial Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009297:Nasal Mucosa / Q000378:metabolism*
D053503:Epithelial Sodium Channels