The epithelial sodium channel: activation by membrane-bound serine proteases.
The epithelial sodium channel (ENaC) was cloned just 10 years ago. Since that time, the study of human monogenic diseases (pseudohypoaldosteronism type 1 [PHA-1] and Liddle syndrome), as well as mouse models mimicking salt-losing syndromes (PHA-1) or salt-sensitive hypertension (Liddle syndrome), have greatly contributed to our understanding of the function of ENaC in vivo. In this brief review, I will first discuss ENaC as a limiting factor in the control of ionic composition of the extracellular fluid and then, more specifically, the activation of ENaC by membrane-bound serine proteases. Recent in vitro and in vivo experiments indicate that membrane-bound serine proteases (channel activating proteases [CAP-1, -2, or-3]) may be of critical importance in the activation of ENaC in different organs, such as the kidney, the lung or the cochlea.
Rossier
Bernard C
BC
Department of Pharmacology, University of Lausanne, Lausanne, Switzerland. Bernard.Rossier@ipharm.unil.ch
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D003051:Cochlea / Q000378:metabolism; D053503:Epithelial Sodium Channels; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism*
D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; C507048:SCNN1B protein, human; D015222:Sodium Channels; D012697:Serine Endopeptidases