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Epithelial Sodium Channel (epithelial + sodium_channel)

Distribution by Scientific Domains

Life Sciences	66%
Medical Sciences	22%

Selected Abstracts

Der Epitheliale Natrium Kanal.

BIOLOGIE IN UNSERER ZEIT (BIUZ), Issue 5 2009
15 Jahre Kanalarbeiten
Abstract Epitheliale Natrium Kanäle (ENaCs) sind Natrium leitende Ionenkanäle, die in der apikalen Membran vieler Epithelien vorkommen. Sie sind der zentrale Faktor zum transepithelialen Transport von Natrium , und damit einhergehend von Wasser. ENaCs tragen zu einer Vielzahl physiologischer Prozesse bei: Regulation des Salz- und Wasserhaushalts, des Blutdrucks oder des Wassergehaltes der Lunge. Auch Erkrankungen wie Bluthochdruck oder Lungenödeme lassen sich auf gestörte Regulationen des ENaC zurückführen. Dieser Artikel beschreibt die Funktion und Physiologie Epithelialer Natrium Kanäle, sowie zelluläre Mechanismen, die die Aktivität dieser Ionenkanäle bestimmen. Epithelial sodium channels (ENaCs) are sodium-conducting ion channels that are located in the apical membrane of various epithelia. They represent the rate-limiting step for transeptihelial sodium- and thereby water-transport. ENaCs contribute to a variety of physiological processes including the regulation of salt and water homeostasis, blood pressure or the water content of the lung. Further, malfunctions in ENaC regulation contribute to the pathogenesis of diseases like hypertension or pulmonary oedema. This article describes the function and physiology of epithelial sodium channels as well as cellular mechanisms that determine the activity of these ion channels. [source]

A novel N-terminal hydrophobic motif mediates constitutive degradation of serum- and glucocorticoid-induced kinase-1 by the ubiquitin,proteasome pathway

FEBS JOURNAL, Issue 13 2006
Agata M. Bogusz
Serum- and glucocorticoid-induced protein kinase-1 (SGK-1) plays a critical role in regulation of the epithelial sodium channel, ENaC. SGK-1 also shares significant catalytic domain homology with protein kinase B (PKB/AKT-1) and is a downstream effector of antiapoptotic phosphoinositide 3-kinase signaling. Steady-state levels of an active SGK-1 are tightly regulated by rapid transcriptional activation and post-translational modification including phosphorylation. We show here that endogenous SGK-1 protein is polyubiquitinated and rapidly degraded by the 26S proteasome. In contrast to other rapidly degraded kinases, neither the catalytic activity of SGK-1 nor activation site phosphorylation was required for its ubiquitin modification and degradation. Instead, SGK-1 degradation required a lysine-less six-amino-acid (amino acids 19,24) hydrophobic motif (GMVAIL) within the N-terminal domain. Deletion of amino acids 19,24 significantly increased the half-life of SGK1 and prevented its ubiquitin modification. Interestingly, this minimal region was also required for the association of SGK-1 with the endoplasmic reticulum. Ubiquitin modification and degradation of SGK-1 were increasingly inhibited by the progressive mutation of six N-terminal lysine residues surrounding the GMVAIL motif. Mutation of all six lysines to arginine did not disrupt the subcellular localization of SGK-1 despite a significant decrease in ubiquitination, implying that this modification per se was not required for targeting to the endoplasmic reticulum. These results suggest that constitutive ubiquitin-mediated degradation of SGK-1 is an important mechanism regulating its biological activity. [source]

Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension

JOURNAL OF NEUROCHEMISTRY, Issue 1 2005
Frank M. Dyka
Abstract Glaucoma is a prevalent cause of blindness, resulting in the apoptotic death of retinal ganglion cells and optic nerve degeneration. The disease is often associated with elevated intraocular pressure, however, molecular mechanisms involved in ganglion cell death are poorly understood. To identify proteins contributing to this pathological process, we analysed the retinal gene expression of DBA/2J mice that develop an elevated intraocular pressure by the age of 6 months with subsequent ganglion cell loss. In this study, we identified subunits of the epithelial sodium channel (ENaC) family that are specifically expressed under elevated intraocular pressure. Using reverse transcriptase polymerase chain reaction we observed a significant increase of ,-ENaC in the neuronal retina of DBA/2J mice when compared with control animals, while ,-ENaC and ,-ENaC were not detectable in this tissue. Specific immune sera to ENaC subunits showed up-regulation of ,-ENaC in synaptic and nuclear layers of the retina, and in the retinal pigment epithelium. Consistent with our polymerase chain reaction data, ,-ENaC was not detected by specific antibodies in the retina, while ,-ENaC was only present in the retinal pigment epithelium under ocular hypertension. Finally, the increase of ,-ENaC gene expression in the neuronal retina and the retinal pigment epithelium was not observed in other tissues of DBA/2J mice. Since the intraocular pressure is regulated by the transport of aqueous humour across epithelial structures of the eye that in turn is associated with ion flux, the specific up-regulation of ENaC proteins could serve as a protecting mechanism against elevated intraocular pressure. [source]

Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome

THE JOURNAL OF PHYSIOLOGY, Issue 2 2008
Marko Bertog
Liddle's syndrome is an autosomal dominant form of human hypertension, caused by gain-of-function mutations of the epithelial sodium channel (ENaC) which is expressed in aldosterone target tissues including the distal colon. We used a mouse model for Liddle's syndrome to investigate ENaC-mediated Na+ transport in late distal colon by measuring the amiloride-sensitive transepithelial short circuit current (,ISC-Ami) ex vivo. In Liddle mice maintained on a standard salt diet, ,ISC-Ami was only slightly increased but plasma aldosterone (PAldo) was severely suppressed. Liddle mice responded to a low or a high salt diet by increasing or decreasing, respectively, their PAldo and ,ISC-Ami. However, less aldosterone was required in Liddle animals to achieve similar or even higher Na+ transport rates than wild-type animals. Indeed, the ability of aldosterone to stimulate ,ISC-Ami was about threefold higher in Liddle animals than in the wild-type controls. Application of aldosterone to colon tissue in vitro confirmed that ENaC stimulation by aldosterone was not only preserved but enhanced in Liddle mice. Aldosterone-induced transcriptional up-regulation of the channel's ,- and ,-subunit (,ENaC and ,ENaC) and of the serum- and glucocorticoid-inducible kinase 1 (SGK1) was similar in colon tissue from Liddle and wild-type animals, while aldosterone had no transcriptional effect on the ,-subunit (,ENaC). Moreover, Na+ feedback regulation was largely preserved in colon tissue of Liddle animals. In conclusion, we have demonstrated that in the colon of Liddle mice, ENaC-mediated Na+ transport is enhanced with an increased responsiveness to aldosterone. This may be pathophysiologically relevant in patients with Liddle's syndrome, in particular on a high salt diet, when suppression of PAldo is likely to be insufficient to reduce Na+ absorption to an appropriate level. [source]

CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
G. Nagel
The cystic fibrosis transmembrane conductance regulator (CFTR) plays a crucial role in regulating fluid secretion by the airways, intestines, sweat glands and other epithelial tissues. It is well established that the CFTR is a cAMP-activated, nucleotide-dependent anion channel, but additional functions are often attributed to it, including regulation of the epithelial sodium channel (ENaC). The absence of CFTR-dependent ENaC inhibition and the resulting sodium hyperabsorption were postulated to be a major electrolyte transport abnormality in cystic fibrosis (CF)-affected epithelia. Several ex vivo studies, including those that used the Xenopus oocyte expression system, have reported ENaC inhibition by activated CFTR, but contradictory results have also been obtained. Because CFTR,ENaC interactions have important implications in the pathogenesis of CF, the present investigation was undertaken by our three independent laboratories to resolve whether CFTR regulates ENaC in oocytes and to clarify potential sources of previously reported dissimilar observations. Using different experimental protocols and a wide range of channel expression levels, we found no evidence that activated CFTR regulates ENaC when oocyte membrane potential was carefully clamped. We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough. We suggest that the inhibitory effect of CFTR on ENaC reported in some earlier oocyte studies could be attributed to problems arising from high levels of channel expression and suboptimal recording conditions, that is, large series resistance and/or insufficient feedback voltage gain. [source]

Expression of water and ion transporters in tracheal aspirates from neonates with respiratory distress

ACTA PAEDIATRICA, Issue 11 2009
Yanhong Li
Abstract Aim:, The aim of the study was to determine whether neonatal respiratory distress is related to changes in water and ion transporter expression in lung epithelium. Methods:, The study included 32 neonates on mechanical ventilation: 6 patients with normal lung X-rays (control group), eight with respiratory distress syndrome (RDS), eight with transient tachypnea of the newborn (TTN), 10 with abnormal lung X-rays (mixed group). The protein abundance of water channel AQP5, epithelial sodium channel (ENaC; ,-, ,- and ,-ENaC) and Na+, K+ -ATPase ,1 were examined in tracheal aspirates using semiquantitative immunoblotting. Results:, ,-ENaC level was significantly lower in RDS group compared with infants with TTN and infants in the control group. AQP5 expression was significantly higher in TTN compared with the infants with RDS and all other infants with abnormal lung X-rays. Conclusion:, Neonatal respiratory distress is associated with changes in ,-ENaC and AQP5 expression. The lower ,-ENaC expression may be one of the factors that predispose to the development of RDS. The higher AQP5 expression may provide the possibility for reabsorption of postnatal lung liquid, which contributes to quick recovery of infants with TTN. [source]

REGULATION OF EPITHELIAL Na+ CHANNELS BY ALDOSTERONE: ROLE OF Sgk1

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2008
Il-Ha Lee
SUMMARY 1The epithelial sodium channel (ENaC) is tightly regulated by hormonal and humoral factors, including cytosolic ion concentration and glucocorticoid and mineralocorticoid hormones. Many of these regulators of ENaC control its activity by regulating its surface expression via neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2). 2During the early phase of aldosterone action, Nedd4-2-dependent downregulation of ENaC is inhibited by the serum- and glucocorticoid-induced kinase 1 (Sgk1). 3Sgk1 phosphorylates Nedd4-2. Subsequently, phosphorylated Nedd4-2 binds to the 14-3-3 protein and, hence, reduces binding of Nedd4-2 to ENaC. 4Nedd4-2 is also phosphorylated by protein kinase B (Akt1). Both Sgk1 and Akt1 are part of the insulin signalling pathway that increases transepithelial Na+ absorption by inhibiting Nedd4-2 and activating ENaC. [source]