scholarly journals Protease stimulation of renal sodium reabsorption in vivo by activation of the collecting duct epithelial sodium channel (ENaC)

2012 ◽  
Vol 28 (4) ◽  
pp. 839-845 ◽  
Author(s):  
Grégory Jacquillet ◽  
Havovi Chichger ◽  
Robert J. Unwin ◽  
David G. Shirley
Keyword(s):  
Sodium Channel ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Renal Sodium Reabsorption ◽  
Epithelial Sodium Channel Enac ◽  
Stimulation Of

Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key renal sodium transporters by chronic insulin infusion in rats

2006 ◽  
Vol 290 (5) ◽  
pp. F1055-F1064 ◽  
Author(s):  
Jian Song ◽  
Xinqun Hu ◽  
Shahla Riazi ◽  
Swasti Tiwari ◽  
James B. Wade ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Channel ◽  
Insulin Infusion ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Kidney Cortex ◽  
Sodium Reabsorption ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Epithelial Sodium Channel Enac

Hyperinsulinemia is associated with hypertension. Dysregulation of renal distal tubule sodium reabsorption may play a role. We evaluated the regulation of the epithelial sodium channel (ENaC) and the thiazide-sensitive Na-Cl cotransporter (NCC) during chronic hyperinsulinemia in rats and correlated these changes to blood pressure as determined by radiotelemetry. Male Sprague-Dawley rats (∼270 g) underwent one of the following three treatments for 4 wk ( n = 6/group): 1) control; 2) insulin-infused plus 20% dextrose in drinking water; or 3) glucose water-drinking (20% dextrose in water). Mean arterial pressures were increased by insulin and glucose (mmHg at 3 wk): 98 ± 1 (control), 107 ± 2 (insulin), and 109 ± 3 (glucose), P < 0.01. Insulin (but not glucose) increased natriuretic response to benzamil (ENaC inhibitor) and hydrochlorothiazide (NCC inhibitor) on average by 125 and 60%, respectively, relative to control rats, suggesting increased activity of these reabsorptive pathways. Neither insulin nor glucose affected the renal protein abundances of NCC or the ENaC subunits (α, β, and γ) in kidney cortex, outer medulla, or inner medulla in a major way, as determined by immunoblotting. However, insulin and to some extent glucose increased apical localization of these subunits in cortical collecting duct principal cells, as determined by immunoperoxidase labeling. In addition, insulin decreased cortical “with no lysine” kinase (WNK4) abundance (by 16% relative to control), which may have increased NCC activity. Overall, insulin infusion increased blood pressure, and NCC and ENaC activity in rats. Increased apical targeting of ENaC and decreased WNK4 expression may be involved.

scholarly journals Conditional Transgenic Mice for Studying the Role of the Glucocorticoid Receptor in the Renal Collecting Duct

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2202-2210 ◽  
Author(s):  
Aurélie Nguyen Dinh Cat ◽  
Antoine Ouvrard-Pascaud ◽  
François Tronche ◽  
Maud Clemessy ◽  
Daniel Gonzalez-Nunez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucocorticoid Receptor ◽  
Sodium Channel ◽  
Leucine Zipper ◽  
Collecting Duct ◽  
Extracellular Volume ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Renal Collecting Duct

The mineralocorticoid receptor (MR) is a major regulator of renal sodium reabsorption and body fluid homeostasis. However, little is known about glucocorticoid receptor (GR)-dependent renal effects. Glucocorticoids may activate both receptors, so it is difficult to distinguish between MR- and GR-mediated effects in vivo. To overcome this complexity, we used a transgenic mouse model allowing conditional GR overexpression (doxycycline inducible TetON system, Hoxb7 promoter) in the renal collecting duct (CD) to identify GR-regulated genes involved in sodium transport in the CD. In microdissected cortical CD, induction of GR expression led (after 2 d of doxycycline) to increased α-epithelial sodium channel and glucocorticoid-induced leucine zipper and decreased abundance of with-no-lysine kinase 4 transcripts, without modification of Na,K-ATPase, serum- and glucocorticoid-kinase-1, or MR expression. No changes occurred in the upstream distal and connecting tubules [distal convoluted tubule (DCT), connecting tubule (CNT)]. Sodium excretion was unaltered, but the urinary aldosterone concentration was reduced, suggesting compensation of transitory extracellular volume expansion that subsequently disappeared. At steady state, i.e. after 15 d of doxycycline administration, transcript abundance remained altered in the CD, whereas mirror changes appeared in the DCT and CNT. Plasma aldosterone or glucocorticoids and blood pressure were all unaffected. These experiments show that: 1) GR, in addition to MR, controls epithelial sodium channel- and glucocorticoid-induced leucine zipper expression in vivo in the CD; 2) with-no-lysine kinase 4 is negatively controlled by GR; and 3) the DCT and CNT compensate for these alterations to maintain normal sodium reabsorption and blood pressure. These results suggest that enhanced GR expression may contribute to enhanced sodium retention in some pathological situations.

Trypsin can activate the epithelial sodium channel (ENaC) in microdissected mouse distal nephron

2008 ◽  
Vol 295 (4) ◽  
pp. F1052-F1062 ◽  
Author(s):  
Viatcheslav Nesterov ◽  
Anke Dahlmann ◽  
Marko Bertog ◽  
Christoph Korbmacher
Keyword(s):  
Sodium Channel ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Extracellular Proteases ◽  
Whole Cell ◽  
Renal Tubular Cells ◽  
Endogenous Proteases ◽  
Renal Tubular ◽  
Epithelial Sodium Channel Enac

Proteases are involved in the processing and activation of the epithelial sodium channel (ENaC). The aim of the present study was to investigate whether the prototypical serine protease trypsin can activate ENaC in microdissected, split-open mouse renal distal tubules. Whole-cell patch-clamp recordings from principal cells of connecting tubules (CNT) or cortical collecting ducts (CCD) demonstrated that addition of trypsin (20 μg/ml) to the bath solution increased the ENaC-mediated amiloride-sensitive whole cell current (Δ IAmi) in the majority of cells. In contrast, trypsin applied in the presence of an excess of soybean trypsin inhibitor had no stimulatory effect. The Δ IAmi response to trypsin was variable, ranging from no apparent effect to a twofold increase in Δ IAmi with an average stimulatory effect of 31 or 37% in mice on low-Na+ or standard Na+ diet, respectively. In cultured M-1 mouse collecting duct cells, a robust stimulatory effect of trypsin on Δ IAmi was only observed in cells pretreated with protease inhibitors. This suggests that endogenous proteases contribute to ENaC activation in renal tubular cells and that the degree of ENaC prestimulation by endogenous proteases determines the magnitude of the stimulatory response to exogenous trypsin. In conclusion, we provide electrophysiological evidence that trypsin can stimulate ENaC activity in native renal mouse tubules. Thus, in the kidney, ENaC stimulation by extracellular proteases may be a relevant regulatory mechanism in vivo.

scholarly journals Interaction between Epithelial Sodium Channel γ-Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct

2020 ◽  
Vol 31 (5) ◽  
pp. 1009-1023 ◽  
Author(s):  
Ali Sassi ◽  
Yubao Wang ◽  
Alexandra Chassot ◽  
Olga Komarynets ◽  
Isabelle Roth ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Knockout Mice ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Paracellular Permeability ◽  
Sodium Reabsorption ◽  
Kidney Tubule ◽  
Sodium Permeability ◽  
Tubular Lumen ◽  
Renal Collecting Duct

BackgroundWater and solute transport across epithelia can occur via the transcellular or paracellular pathways. Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. In the renal collecting duct, which is a typical absorptive tight epithelium, coordination between transcellular sodium reabsorption and paracellular permeability may prevent the backflow of reabsorbed sodium to the tubular lumen along a steep electrochemical gradient.MethodsTo investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability via modulating expression of the transmembrane protein claudin-8, we used cultured mouse cortical collecting duct cells to see how overexpression or silencing of epithelial sodium channel (ENaC) subunits and claudin-8 affect paracellular permeability. We also used conditional kidney tubule–specific knockout mice lacking ENaC subunits to assess the ENaC’s effect on claudin-8 expression.ResultsOverexpression or silencing of the ENaC γ-subunit was associated with parallel and specific changes in claudin-8 abundance. Increased claudin-8 abundance was associated with a reduction in paracellular permeability to sodium, whereas decreased claudin-8 abundance was associated with the opposite effect. Claudin-8 overexpression and silencing reproduced these functional effects on paracellular ion permeability. Conditional kidney tubule–specific ENaC γ-subunit knockout mice displayed decreased claudin-8 expression, confirming the cell culture experiments' findings. Importantly, ENaC β-subunit or α-subunit silencing or kidney tubule–specific β-ENaC or α-ENaC knockout mice did not alter claudin-8 abundance.ConclusionsOur data reveal the specific coupling between ENaC γ-subunit and claudin-8 expression. This coupling may play an important role in preventing the backflow of reabsorbed solutes and water to the tubular lumen, as well as in coupling paracellular and transcellular sodium permeability.

Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney

2000 ◽  
Vol 279 (1) ◽  
pp. F46-F53 ◽  
Author(s):  
Carolyn A. Ecelbarger ◽  
Gheun-Ho Kim ◽  
James Terris ◽  
Shyama Masilamani ◽  
Carter Mitchell ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Transport ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Acute Administration ◽  
Brattleboro Rats ◽  
Water Restriction ◽  
Short Term

Sodium transport is increased by vasopressin in the cortical collecting ducts of rats and rabbits. Here we investigate, by quantitative immunoblotting, the effects of vasopressin on abundances of the epithelial sodium channel (ENaC) subunits (α, β, and γ) in rat kidney. Seven-day infusion of 1-deamino-[8-d-arginine]-vasopressin (dDAVP) to Brattleboro rats markedly increased whole kidney abundances of β- and γ-ENaC (to 238% and 288% of vehicle, respectively), whereas α-ENaC was more modestly, yet significantly, increased (to 142% of vehicle). Similarly, 7-day water restriction in Sprague-Dawley rats resulted in significantly increased abundances of β- and γ- but no significant change in α-ENaC. Acute administration of dDAVP (2 nmol) to Brattleboro rats resulted in modest, but significant, increases in abundance for all ENaC subunits, within 1 h. In conclusion, all three subunits of ENaC are upregulated by vasopressin with temporal and regional differences. These changes are too slow to play a major role in the short-term action of vasopressin to stimulate sodium reabsorption in the collecting duct. Long-term increases in ENaC abundance should add to the short-term regulatory mechanisms (undefined in this study) to enhance sodium transport in the renal collecting duct.

scholarly journals The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells

2007 ◽  
Vol 282 (52) ◽  
pp. 37402-37411 ◽  
Author(s):  
Warren G. Hill ◽  
Michael B. Butterworth ◽  
Huamin Wang ◽  
Robert S. Edinger ◽  
Jonathan Lebowitz ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Lipid Rafts ◽  
Apical Membrane ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Cortical Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Epithelial Sodium Channel Enac

Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron

2012 ◽  
Vol 303 (9) ◽  
pp. F1289-F1299 ◽  
Author(s):  
Viatcheslav Nesterov ◽  
Anke Dahlmann ◽  
Bettina Krueger ◽  
Marko Bertog ◽  
Johannes Loffing ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Single Channel ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Salt Diet ◽  
Low Salt ◽  
Immunohistochemical Evidence ◽  
Epithelial Sodium Channel Enac

Aldosterone is thought to be the main hormone to stimulate the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). There is immunohistochemical evidence for an axial gradient of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. However, most of our knowledge about renal ENaC function stems from studies in the cortical collecting duct (CCD). Here we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on different sodium diets to vary plasma aldosterone levels. Single-channel recordings demonstrated amiloride-sensitive Na+ channels in DCT2/CNT with biophysical properties typical for ENaC previously described in CNT/CCD. In animals maintained on a standard salt diet, the average ENaC-mediated whole cell current (Δ Iami) was higher in DCT2/CNT than in CNT/CCD. A low salt diet increased Δ Iami in CNT/CCD but had little effect on Δ Iami in DCT2/CNT. To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS−/−) mice that lack aldosterone. In CNT/CCD of AS−/− mice, Δ Iami was lower than that in wild-type (WT) animals and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS−/− mice, Δ Iami was similar to that in DCT2/CNT of WT animals both on a standard and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely independent of aldosterone which is in contrast to its known aldosterone sensitivity in CNT/CCD.

scholarly journals Phosphatidylinositol 3,4,5-Trisphosphate Mediates Aldosterone Stimulation of Epithelial Sodium Channel (ENaC) and Interacts with γ-ENaC

2005 ◽  
Vol 280 (49) ◽  
pp. 40885-40891 ◽  
Author(s):  
My N. Helms ◽  
Lian Liu ◽  
You-You Liang ◽  
Otor Al-Khalili ◽  
Alain Vandewalle ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Epithelial Sodium Channel ◽  
Epithelial Sodium Channel Enac ◽  
Stimulation Of
Sign in / Sign up

Export Citation Format

Share Document