The Epithelial Sodium Channel: Activation by Membrane-Bound Serine Proteases

2004 ◽  
Vol 1 (1) ◽  
pp. 4-9 ◽  
Author(s):  
B. C. Rossier
Keyword(s):  
Sodium Channel ◽  
Serine Proteases ◽  
Epithelial Sodium Channel ◽  
Channel Activation ◽  
Sodium Channel Activation ◽  
Membrane Bound

scholarly journals Azithromycin Inhibits Constitutive Airway Epithelial Sodium Channel Activation in Vitro and Modulates Downstream Pathogenesis in Vivo

2020 ◽  
Vol 43 (4) ◽  
pp. 725-730 ◽  
Author(s):  
Haruka Fujikawa ◽  
Taise Kawakami ◽  
Ryunosuke Nakashima ◽  
Aoi Nasu ◽  
Shunsuke Kamei ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Epithelial Sodium Channel ◽  
Airway Epithelial ◽  
Channel Activation ◽  
Sodium Channel Activation

scholarly journals Inter-α-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in ΔF508 Mice

2014 ◽  
Vol 50 (5) ◽  
pp. 953-962 ◽  
Author(s):  
Ahmed Lazrak ◽  
Asta Jurkuvenaite ◽  
Emily C. Ness ◽  
Shaoyan Zhang ◽  
Bradford A. Woodworth ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Epithelial Sodium Channel ◽  
Channel Activation ◽  
Sodium Channel Activation

Terfenadine prevents NMDA receptor-dependent and -independent toxicity following sodium channel activation

1999 ◽  
Vol 842 (2) ◽  
pp. 478-481 ◽  
Author(s):  
Ramón Dı́az-Trelles ◽  
Antonello Novelli ◽  
Giulia Puia ◽  
M.Teresa Fernández-Sánchez
Keyword(s):  
Nmda Receptor ◽  
Sodium Channel ◽  
Channel Activation ◽  
Sodium Channel Activation

scholarly journals TMPRSS4-dependent activation of the epithelial sodium channel requires cleavage of the γ-subunit distal to the furin cleavage site

2012 ◽  
Vol 302 (1) ◽  
pp. F1-F8 ◽  
Author(s):  
Christopher J. Passero ◽  
Gunhild M. Mueller ◽  
Michael M. Myerburg ◽  
Marcelo D. Carattino ◽  
Rebecca P. Hughey ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Cleavage Site ◽  
Epithelial Sodium Channel ◽  
Cleavage Sites ◽  
Furin Cleavage ◽  
Channel Activation ◽  
Α Subunit ◽  
Γ Subunit ◽  
Furin Cleavage Site ◽  
Unique Mechanism

The epithelial sodium channel (ENaC) is activated by a unique mechanism, whereby inhibitory tracts are released by proteolytic cleavage within the extracellular loops of two of its three homologous subunits. While cleavage by furin within the biosynthetic pathway releases one inhibitory tract from the α-subunit and moderately activates the channel, full activation through release of a second inhibitory tract from the γ-subunit requires cleavage once by furin and then at a distal site by a second protease, such as prostasin, plasmin, or elastase. We now report that coexpression of mouse transmembrane protease serine 4 (TMPRSS4) with mouse ENaC in Xenopus oocytes was associated with a two- to threefold increase in channel activity and production of a unique ∼70-kDa carboxyl-terminal fragment of the γ-subunit, similar to the ∼70-kDa γ-subunit fragment that we previously observed with prostasin-dependent channel activation. TMPRSS4-dependent channel activation and production of the ∼70-kDa fragment were partially blocked by mutation of the prostasin-dependent cleavage site (γRKRK186QQQQ). Complete inhibition of TMPRSS4-dependent activation of ENaC and γ-subunit cleavage was observed when three basic residues between the furin and prostasin cleavage sites were mutated (γK173Q, γK175Q, and γR177Q), in addition to γRKRK186QQQQ. Mutation of the four basic residues associated with the furin cleavage site (γRKRR143QQQQ) also prevented TMPRSS4-dependent channel activation. We conclude that TMPRSS4 primarily activates ENaC by cleaving basic residues within the tract γK173-K186 distal to the furin cleavage site, thereby releasing a previously defined key inhibitory tract encompassing γR158-F168 from the γ-subunit.

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