Functional Domains of the Epithelial Sodium Channel

Loffing, Johannes; Schild, Laurent

doi:10.1681/asn.2005050456

Cited by 30 publications

(27 citation statements)

References 70 publications

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“…Using an antibody directed against γ-ENaC, typical ENaC staining 28 was detected along the entire ASDN of WT and L/L animals under all dietary conditions used (Figures 4; Figure S1). Only a minority of ASDN cells, likely to be intercalated cells, did not show ENaC staining.…”

Section: The Liddle Syndrome Mutation Enhances the Apical Localizatiomentioning

confidence: 99%

In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron

et al. 2016

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The epithelial sodium channel (ENaC) is rate limiting for Na + absorption in the aldosterone-sensitive distal nephron comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT), and the entire collecting duct. Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. In the cortical collecting duct (CCD), ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone-independent ENaC regulation in the early part of the aldosterone-sensitive distal nephron. Here, we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice homozygous for Liddle syndrome mutation or from wild-type control mice. Whole-cell patch-clamp recordings were used to measure amiloride-sensitive ENaC currents in nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that in mice with Liddle syndrome, the primary site of increased Na + reabsorption is the DCT2/CNT. In addition, increased aldosterone responsiveness of ENaC in CNT/CCD may contribute to salt-sensitive hypertension in Liddle syndrome. Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. Our findings highlight the importance of ENaC function and regulation in the early part of the aldosterone-sensitive distal nephron for the maintenance of sodium balance and blood pressure control.

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Section: The Liddle Syndrome Mutation Enhances the Apical Localizatiomentioning

confidence: 99%

In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron

et al. 2016

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“…NIF ϩ SPR did prevent the increased PVE and medullary ␣-ENaC protein abundance, suggesting that aldosterone mediates the increased ENaC abundance in medulla (as anticipated), which plays a primary role in the sodium retention leading to PVE. Although ENaC is responsible for only ϳ2% of sodium reabsorption, the collecting duct is the principal site of determination of net sodium balance (16,18). Furthermore, we recently demonstrated that ENaC activity is necessary for maintenance of PVE in the late pregnant rat (38).…”

Section: Discussionmentioning

confidence: 95%

Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways

West

Shaw

Sasser

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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West CA, Shaw S, Sasser JM, Fekete A, Alexander T, Cunningham MW Jr, Masilamani SM, Baylis C. Chronic vasodilation increases renal medullary PDE5A and ␣-ENaC through independent renin-angiotensin-aldosterone system pathways. via diet], enalapril (ENAL; angiotensin-converting enzyme inhibitor, 62.5 mg/l via water), or vehicle (CON). Mean arterial pressure (MAP) was reduced 7.4 Ϯ 0.5% with NIF, 6.33 Ϯ 0.5% with NIF ϩ SPR, 13.3 Ϯ 0.9% with NIF ϩ LOS, and 12.0 Ϯ 0.4% with ENAL vs. baseline MAP. Compared with CON (3.6 Ϯ 0.3%), plasma volume factored for body weight was increased by NIF (5.2 Ϯ 0.4%) treatment but not by NIF ϩ SPR (4.3 Ϯ 0.3%), NIF ϩ LOS (3.6 Ϯ 0.1%), or ENAL (4.0 Ϯ 0.3%). NIF increased PDE5A protein abundance in the renal inner medulla, and SPR did not prevent this increase (188 Ϯ 16 and 204 Ϯ 22% of CON, respectively). NIF increased the ␣-subunit of the epithelial sodium channel (␣-ENaC) protein in renal outer (365 Ϯ 44%) and inner (526 Ϯ 83%) medulla, and SPR prevented these changes. There was no change in either PDE5A or ␣-ENaC abundance vs. CON in rats treated with NIF ϩ LOS or ENAL. These data indicate that the PVE and renal medullary adaptations in response to chronic vasodilation result from RAAS signaling, with increases in PDE5A mediated through AT 1 receptor and ␣-ENaC through the MR.

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“…The StV is bound by several types of parasensory epithelium. Previously is has been suggested that several different ion channels are present in these parasensory epithelium cells, which include the IsK/KvLQT1, Ca 2+ -activated nonselective cation, Cl -and ENaC channels (12,18). The IsK/KvLQT1 channel has been shown to be the main pathway across the apical membrane of strial marginal cells for secreting K + into the lumen of the inner ear.…”

Section: Discussionmentioning

confidence: 99%

“…Together with basolateral Na + /K + -ATPase, ENaC regulates sodium reabsorption and plays a major role in the control of total body salt and water homeostasis (12). In numerous types of cells, it has been shown that ENaC is regulated by a variety of extrinsic factors, such as proteolytic cleavage, mechanical and cytoskeletal activity.…”

Section: Discussionmentioning

confidence: 99%

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Atrial natriuretic peptide reduces the α-subunit of the epithelial sodium channel mRNA expression in the mouse stria vascularis

Luo

Xia

et al. 2014

Biomedical Reports

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Abstract. Atrial natriuretic peptide (ANP) is extensively expressed in the cochlea, including the strial vascularis (StV). ANP may participate in the regulation of the water-electrolyte balance. However, the functional significance of ANP in the cochlea is less understood and little is known regarding the exact mechanisms. Studies suggest that the epithelial sodium channel (ENaC) is important for regulating sodium transport across epithelia. ENaC may be involved in the clearance of endolymphatic Na + and maintenance of a K-rich and Na-poor composition in the endolymph. Whether ANP has a regulatory effect on the Na + channel in the StV remains unknown. The aim of the present study was to evaluate whether ANP affects the expression of the α-subunit of the ENaC (α-ENaC) mRNA in the mouse StV, using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technique. The mouse StV tissues were incubated with 10 -6 mol/l ANP for different times (2, 6, 12, 24 and 48 h) and were subsequently harvested. α-ENaC mRNA was extracted for RT-qPCR analysis of the expression. The study demonstrated the existence of α-ENaC in the mouse StV. Tissues treated with ANP (10 -6 mol/l) showed a significant reduction in α-ENaC mRNA expression (n=3, P<0.05). A maximum effect was reached at 2 h after treatment. The present results indicate that ANP may regulate cochlear ion transport and endolymph fluid balance in the inner ear via reducing expression of the α-ENaC mRNA in the mouse StV. IntroductionAtrial natriuretic peptide (ANP), which was first extracted from rat atrial tissue by Baines et al, is now known to be a member of the natriuretic peptide family (1). The natriuretic peptide family consists of a family of 5 natriuretic peptides that include A-, B-, C-type natriuretic peptide, urodilatin and Dendroaspis natriuretic peptide (2). The pathophysiological actions of various natriuretic peptides are mediated by three different natriuretic peptide receptors; atrial natriuretic peptide receptor-A-type (NPR-A), NPR-B-and NPR-C (3). ANP, an A-type natriuretic peptide, has been reported to have a wide variety of biological functions, not only in the circulatory system but also in the kidney and other tissues (3). ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure.ANP receptors are distributed extensively in the cochlea, including the strial vascularis (StV). Lamprecht and Meyer zum Gottesberge (4) first reported that ANP receptors are expressed in the inner ear of guinea pigs. Previous studies have also identified ANP receptors in the inner ear of guinea pigs and rats, and demonstrated their presence in the StV, spiral ligament in the cochlea and the secretory epithelium of the vestibular organ (4-10).Studies suggest that ANP may be locally synthesized and activates NPR-A in a paracrine/autocrine manner (4-8). Pronounced immunoreactivity for ANP was observed in the spiral ligament of the cochlear lateral wall. ANP has been demonstrated to be expressed mainly i...

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Functional Domains of the Epithelial Sodium Channel

Cited by 30 publications

References 70 publications

In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron

In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron

Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways

Atrial natriuretic peptide reduces the α-subunit of the epithelial sodium channel mRNA expression in the mouse stria vascularis

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