Regulation of the epithelial sodium channel (ENaC) by hormonal and local mediators
The epithelial sodium channel (ENaC) is a member of the ENaC/degenerin family of ion channels. ENaC is localized in the apical membrane of epithelial cells and is the rate limiting step for sodium absorption in epithelial tissues including the aldosterone-sensitive distal nephron (ASDN), the distal colon and respiratory epithelia. Abnormal ENaC activation in the ASDN may cause renal sodium retention and arterial hypertension. This is evidenced by gain-of-function mutations of ENaC which cause Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension. In the ASDN hormonal and local mediators contribute to ENaC regulation in a highly complex manner with aldosterone-dependent and -independent mechanisms. A unique feature of ENaC is its proteolytic activation which involves specific cleavage sites and the release of inhibitory peptide fragments. Under pathophysiological conditions abnormal ENaC activation by urinary proteases may contribute to sodium retention in nephrotic syndrome. The identity of physiologically relevant tubular proteases involved in proteolytic ENaC activation remains to be elucidated. In addition, renal interstitial proteases may stimulate ENaC mediated transepithelial transport through PAR2 (protease-activated receptor 2) localized in the basolateral membrane of tubular epithelial cells. This may be relevant in inflammatory renal disease. Recently, bile acids known to activate BASIC (bile acid-sensitive ion channel), another member of the ENaC/degenerin family of ion channels, have been shown to modify ENaC function. It is tempting to speculate that bile acids or other endogenous amphiphilic substances may affect ENaC function by interacting with specific channel regions.
Date: 16 February 2018, 13:00 (Friday, 5th week, Hilary 2018)
Venue: Sherrington Building, off Parks Road OX1 3PT
Venue Details: Large Lecture Theatre
Speaker: Professor Christoph Korbmacher (Friedrich-Alexander-Universität Erlangen-Nürnberg)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organiser: Sally Collins (University of Oxford)
Organiser contact email address:
Host: Professor Anant Parekh (University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Sally Collins