Role of Mineralocorticoid receptor (MR) and NEDD4‐2 in the regulation of ENaC and ROMK in the Distal Convoluted Tubule (DCT) and Cortical Collecting Duct (CCD)

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Dandan Zhang ◽  
Peng Wu ◽  
Xin-Peng Duan ◽  
Dao-Hong Lin ◽  
Olivier Staub ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Collecting Duct ◽  
Distal Convoluted Tubule ◽  
Cortical Collecting Duct

scholarly journals Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K+ intake on ROMK channel in the distal convoluted tubule

2018 ◽  
Vol 315 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
Peng Wu ◽  
Zhong-Xiuzi Gao ◽  
Xiao-Tong Su ◽  
David H. Ellison ◽  
Juliette Hadchouel ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Collecting Duct ◽  
Distal Convoluted Tubule ◽  
Cortical Collecting Duct ◽  
Cell Models ◽  
High K ◽  
Cell Recording ◽  
Clearance Study ◽  
Stimulation Of

With-no-lysine kinase 4 (WNK4) and kidney-specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring tertiapin-Q (TPNQ; ROMK inhibitor)-sensitive K+ currents with whole cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS- WNK1−/− and WNK4−/− mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited. Moreover, WNK4−/− mice were hypokalemic, while KS- WNK1−/− mice had normal plasma K+ levels. High K+ (HK) intake significantly increased TPNQ-sensitive K+ currents in DCT2/CNT of WT and WNK4−/− mice but not in KS- WNK1−/− mice. However, TPNQ-sensitive K+ currents in the cortical collecting duct (CCD) were normal not only under control conditions but also significantly increased in response to HK in KS- WNK1−/− mice. This suggests that the deletion of KS-WNK1-induced inhibition of ROMK occurs only in the DCT2/CNT. Renal clearance study further demonstrated that the deletion of KS-WNK1 did not affect the renal ability of K+ excretion under control conditions and during increasing K+ intake. Also, HK intake did not cause hyperkalemia in KS- WNK1−/− mice. We conclude that KS-WNK1 but not WNK4 is required for HK intake-induced stimulation of ROMK activity in DCT2/CNT. However, KS-WNK1 is not essential for HK-induced stimulation of ROMK in the CCD, and the lack of KS-WNK1 does not affect net renal K+ excretion.

scholarly journals Effect of Angiotensin II on ENaC in the Distal Convoluted Tubule and in the Cortical Collecting Duct of Mineralocorticoid Receptor Deficient Mice

2020 ◽  
Vol 9 (7) ◽  
Author(s):  
Peng Wu ◽  
Zhong‐Xiuzi Gao ◽  
Dan‐Dan Zhang ◽  
Xin‐Peng Duan ◽  
Andrew S. Terker ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mineralocorticoid Receptor ◽  
Sodium Intake ◽  
Collecting Duct ◽  
Distal Convoluted Tubule ◽  
Cortical Collecting Duct ◽  
Wild Type ◽  
Low Sodium ◽  
High K ◽  
Independent Mechanism

Background Angiotensin II stimulates epithelial Na + channel (ENaC) by aldosterone‐independent mechanism. We now test the effect of angiotensin II on ENaC in the distal convoluted tubule (DCT) and cortical collecting duct (CCD) of wild‐type (WT) and kidney‐specific mineralocorticoid receptor knockout mice (KS‐MR‐KO). Methods and Results We used electrophysiological, immunoblotting and renal‐clearance methods to examine the effect of angiotensin II on ENaC in KS‐MR‐KO and wild‐type mice. High K + intake stimulated ENaC in the late DCT/early connecting tubule (DCT2/CNT) and in the CCD whereas low sodium intake stimulated ENaC in the CCD but not in the DCT2/CNT. The deletion of MR abolished the stimulatory effect of high K + and low sodium intake on ENaC, partially inhibited ENaC in DCT2/CNT but almost abolished ENaC activity in the CCD. Application of losartan inhibited ENaC only in DCT2/CNT of both wild‐type and KS‐MR‐KO mice but not in the CCD. Angiotensin II infusion for 3 days has a larger stimulatory effect on ENaC in the DCT2/CNT than in the CCD. Three lines of evidence indicate that angiotensin II can stimulate ENaC by MR‐independent mechanism: (1) angiotensin II perfusion augmented ENaC expression in KS‐MR‐KO mice; (2) angiotensin II stimulated ENaC in the DCT2/CNT but to a lesser degree in the CCD in KS‐MR‐KO mice; (3) angiotensin II infusion augmented benzamil‐induced natriuresis, increased the renal K + excretion and corrected hyperkalemia of KS‐MR‐KO mice. Conclusions Angiotensin II‐induced stimulation of ENaC occurs mainly in the DCT2/CNT and to a lesser degree in the CCD and MR plays a dominant role in determining ENaC activity in the CCD but to a lesser degree in the DCT2/CNT.

Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

Role of AQP2 during apoptosis in cortical collecting duct cells

2009 ◽  
Vol 101 (4) ◽  
pp. 237-250 ◽  
Author(s):  
Pilar Flamenco ◽  
Luciano Galizia ◽  
Valeria Rivarola ◽  
Juan Fernandez ◽  
Paula Ford ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

Critical role of the mineralocorticoid receptor in aldosterone-dependent and aldosterone-independent regulation of ENaC in the distal nephron

2021 ◽  
Author(s):  
Viatcheslav Nesterov ◽  
Marko Bertog ◽  
Jérémie Canonica ◽  
Edith Hummler ◽  
Richard Coleman ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Collecting Duct ◽  
Critical Role ◽  
Sodium Absorption ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Patch Clamp Technique ◽  
Transition Zones ◽  
Rate Limiting Step

The epithelial sodium channel (ENaC) constitutes the rate-limiting step for sodium absorption in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the collecting duct. Previously, we demonstrated that ENaC activity in the DCT2/CNT transition zone is constitutively high and independent of aldosterone, in contrast to its aldosterone dependence in the late CNT and initial cortical collecting duct (CNT/CCD). The mineralocorticoid receptor (MR) is expressed in the entire ASDN. Its activation by glucocorticoids is prevented through 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) abundantly expressed in the late but probably not the early part of ASDN. We hypothesized that ENaC function in the early part of the ASDN is aldosterone-independent but may depend on MR activated by glucocorticoids due to low 11β-HSD2 abundance. To test this hypothesis, we used doxycycline-inducible nephron-specific MR-deficient mice (MR KO). Whole-cell ENaC currents were investigated in isolated nephron fragments from DCT2/CNT or CNT/CCD transition zones using the patch-clamp technique. ENaC activity was detectable in CNT/CCD of control mice but absent or barely detectable in the majority of CNT/CCD preparations from MR KO mice. Importantly, ENaC currents in DCT2/CNT were greatly reduced in MR KO mice compared to ENaC currents in DCT2/CNT of control mice. Immunofluorescence for 11β-HSD2 was abundant in CCD, less prominent in CNT and very low in DCT2. We conclude that MR is critically important for maintaining aldosterone-independent ENaC activity in DCT2/CNT. Aldosterone-independent MR activation is probably mediated by glucocorticoids due to low expression of 11β-HSD2.

Evidence of corticosteroid action along the nephron

1984 ◽  
Vol 246 (2) ◽  
pp. F111-F123 ◽  
Author(s):  
D. Marver
Keyword(s):  
Collecting Duct ◽  
Type I ◽  
Type Ii ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Type Iii ◽  
Collecting Ducts ◽  
Collecting Tubule ◽  
Cortical Collecting Tubule

The kidney contains three classes of corticosteroid-binding proteins receptors. They include a mineralocorticoid-specific (Type I), a glucocorticoid-specific (Type II), and a corticosterone-specific (Type III) site. The Type I and Type III sites roughly parallel each other along the nephron, with maximal binding occurring in the late distal convoluted or connecting segment and the cortical and medullary collecting ducts. Type II sites occur throughout the nephron, with maximal concentrations appearing in the proximal tubule and the late distal convoluted-cortical collecting duct region. The function of the Type I sites in the connecting segment is unclear since chronic mineralocorticoid therapy does not influence the potential difference in this segment as it does in the cortical collecting tubule. Furthermore, the specific role of Type II versus Type III sites in the distal nephron is unknown. Finally, the possible influence of sodium on both latent and steroid-induced renal cortical and medullary Na-K-ATPase is discussed.

Adaptation to alkalosis induces cell cycle delay and apoptosis in cortical collecting duct cells: Role of aquaporin-2

2010 ◽  
Vol 224 (2) ◽  
pp. 405-413 ◽  
Author(s):  
Valeria Rivarola ◽  
Pilar Flamenco ◽  
Luciana Melamud ◽  
Luciano Galizia ◽  
Paula Ford ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Cell Cycle Delay ◽  
Aquaporin 2 ◽  
Duct Cells ◽  
Collecting Duct Cells

A mathematical model of rat distal convoluted tubule. II. Potassium secretion along the connecting segment

2005 ◽  
Vol 289 (4) ◽  
pp. F721-F741 ◽  
Author(s):  
Alan M. Weinstein
Keyword(s):  
Water Permeability ◽  
Collecting Duct ◽  
Cell Types ◽  
Distal Convoluted Tubule ◽  
Cortical Collecting Duct ◽  
Transport Activity ◽  
Luminal Membrane ◽  
In Series ◽  
Potassium Secretion ◽  
Osmotic Equilibration

A simulation of the rat distal convoluted tubule (DCT) is completed with a model of the late portion, or connecting tubule (CNT). This CNT model is developed by relying on a prior cortical collecting duct (CCD) model (Weinstein AM. Am J Physiol Renal Physiol 280: F1072–F1092, 2001), and scaling up transport activity of the three cell types to a level appropriate for DCT. The major difference between the two tubule segments is the lower CNT water permeability. In early CNT the luminal solution is hypotonic, with a K+ concentration less than that of plasma, and it is predicted that osmotic equilibration requires the whole length of CNT, to end with a nearly isotonic fluid, whose K+ concentration is severalfold greater than plasma. With respect to potassium secretion, early CNT conditions are conducive to maximal fluxes, whereas late conditions require the capacity to transport against a steep electrochemical gradient. The parameter dependence for K+ secretion under each condition is different: maximal secretion depends on luminal membrane K+ permeability, but the limiting luminal K+ concentration does not. However, maximal secretion and the limiting gradient are both enhanced by greater Na+ reabsorption. While higher CNT water permeability depresses K+ secretion, it favors Na+ reabsorption. Thus in antidiuresis there is a trade-off between enhanced Na+-dependent K+ secretion and the attenuation of K+ secretion by slow flow. When the CNT model is configured in series with the early DCT, thiazide diuretics promote renal K+ wasting by shifting Na+ reabsorption from early DCT to CNT; they promote alkalosis by shifting the remaining early DCT Na+ reabsorption to Na+/H+ exchange. This full DCT is suitable for simulating the defects of hyperkalemic hypertension, but the model offers no suggestion of a tight junction abnormality that might contribute to the phenotype.

Deoxycorticosterone-stimulated bicarbonate secretion in rabbit cortical collecting ducts: effects of luminal chloride removal and in vivo acid loading

1985 ◽  
Vol 249 (2) ◽  
pp. F205-F212 ◽  
Author(s):  
J. Garcia-Austt ◽  
D. W. Good ◽  
M. B. Burg ◽  
M. A. Knepper
Keyword(s):  
Collecting Duct ◽  
High Rate ◽  
Bicarbonate Secretion ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Urinary Ph ◽  
Collecting Ducts ◽  
Acid Loading

To assess the role of cortical collecting duct bicarbonate secretion in the regulation of net acid excretion, we have sought to identify what factors influence the secretion rate. Net and unidirectional bicarbonate fluxes were measured in isolated perfused cortical collecting ducts from deoxycorticosterone-treated rabbits. The collecting ducts secreted bicarbonate at 11-24 pmol X mm-1 X min-1, confirming the high rate seen in earlier studies. Oral acid loading (50 mM NH4Cl drinking water) completely inhibited the net bicarbonate secretion. The bath-to-lumen flux was markedly reduced with acid loading, but the lumen-to-bath flux changed very little. In tubules from rabbits treated with deoxycorticosterone (but not NH4Cl), luminal chloride replacement with either sulfate or gluconate completely and reversibly inhibited the net bicarbonate secretion. The bath-to-lumen flux was greatly inhibited, but there was little change in the lumen-to-bath flux. We conclude: 1) High rates of bicarbonate secretion can be induced in rabbit cortical collecting ducts by chronic treatment of the animals with deoxycorticosterone. 2) When deoxycorticosterone-treated rabbits were made acidotic by oral administration of NH4Cl, the bicarbonate secretion was prevented, indicating that the systemic acid-base state of the animal may be an important factor regulating bicarbonate secretion. 3) Replacement of chloride in the lumen with sulfate inhibits bicarbonate secretion in the cortical collecting duct, an effect which may explain in part the decrease in urinary pH in response to sulfate infusions in mineralocorticoid-stimulated animals.

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