title: Feedback inhibition of ENaC during acute sodium loading in vivo.
abstract: The epithelial Na(+) channel (ENaC) is tightly regulated by sodium intake to maintain whole body sodium homeostasis. In addition, ENaC is inhibited by high levels of intracellular Na(+) [Na(+)](i), presumably to prevent cell Na(+) overload and swelling. However, it is not clear if this regulation is relevant in vivo. We show here that in rats, an acute (4 h) oral sodium load decreases whole-cell amiloride-sensitive currents (I(Na)) in the cortical collecting duct (CCD) even when plasma aldosterone levels are maintained high by infusing the hormone. This was accompanied by decreases in whole-kidney cleaved α-ENaC (2.6 fold), total β-ENaC (1.7 fold), and cleaved γ-ENaC (6.2 fold). In addition, cell-surface β- and γ-ENaC expression was measured using in situ biotinylation. There was a decrease in cell-surface core-glycosylated (2.2 fold) and maturely glycosylated (4.9 fold) β-ENaC and cleaved γ-ENaC (4.7 fold). There were no significant changes for other apical sodium transporters. To investigate the role of increases in Na(+) entry and presumably [Na(+)](i) on ENaC, animals were infused with amiloride prior to and during sodium loading. Blocking Na(+) entry did not inhibit the effect of resalting on I(Na). However, amiloride did prevent decreases in ENaC expression, an effect that was not mimicked by hydrochlorothiazide administration. Na(+) entry and presumably [Na(+)](i) can regulate ENaC expression but does not fully account for the aldosterone-independent decrease in I(Na) during an acute sodium load.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Ankit B
authors.initials: AB
authors.lastname: Patel
authors.forename: Gustavo
authors.initials: G
authors.lastname: Frindt
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Palmer
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004232:Diuretics / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D014867:Water / Q000737:chemistry / Q000378:metabolism; D014882:Water-Electrolyte Balance
chemical_list: D004232:Diuretics; D053503:Epithelial Sodium Channels; D014867:Water; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium