Role of proteolysis in the activation of epithelial sodium channels.
OBJECTIVE
Epithelial sodium channels mediate Na+ transport across high resistance, Na+-transporting epithelia. This review describes recent findings that indicate that epithelial sodium channels are activated by the proteolytic release of inhibitory peptides from the alpha and gamma subunits.


RESULTS
Non-cleaved channels have a low intrinsic open probability that may reflect enhanced channel inhibition by external Na+--a process referred to as Na+ self-inhibition. Cleavage at a minimum of two sites within the alpha or gamma subunits is required to activate the channel, presumably by releasing inhibitory fragments. The extent of epithelial sodium channel proteolysis is dependent on channel residency time at the plasma membrane, as well as on the balance between levels of expression of proteases that activate epithelial sodium channels and inhibitors of these proteases. Regulated epithelial sodium channel proteolysis has been observed in rat kidney and in human airway epithelia.


CONCLUSIONS
Proteolysis of epithelial sodium channel subunits plays a key role in modulating epithelial sodium channel activity through changes in channel open probability.
Hughey
Rebecca P
RP
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Carattino
Marcelo D
MD
Kleyman
Thomas R
TR
D000818:Animals; D001692:Biological Transport; D001980:Bronchi / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D045683:Furin / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D011336:Probability; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000737:chemistry; D015222:Sodium Channels / Q000737:chemistry*
D011480:Protease Inhibitors; D015222:Sodium Channels; D012964:Sodium; D010447:Peptide Hydrolases; D045683:Furin