Gene Symbol: Scnn1b
Description: sodium channel epithelial 1 beta subunit
Alias: RNENACB, amiloride-sensitive sodium channel subunit beta, SCNEB, beta-ENaC, beta-NaCH, epithelial Na(+) channel subunit beta, nonvoltage-gated sodium channel 1 subunit beta, sodium channel, non-voltage-gated 1, beta subunit, sodium channel, nonvoltage-gated 1, beta, sodium channel, nonvoltage-gated, type I, beta
Species: rat
Products:     Scnn1b

Top Publications

  1. Staub O, Dho S, Henry P, Correa J, Ishikawa T, McGlade J, et al. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J. 1996;15:2371-80 pubmed
    ..These results demonstrate that the WW domains of rNedd4 bind to the PY motifs deleted from beta or gammaENaC in Liddle's syndrome patients, and suggest that Nedd4 may be a regulator (suppressor) of the epithelial Na+ channel. ..
  2. Lu C, Pribanic S, Debonneville A, Jiang C, Rotin D. The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. Traffic. 2007;8:1246-64 pubmed
    ..These results suggest that the ENaC PY motifs (and Nedd4-2) primarily regulate channel internalization but also affect cAMP-dependent replenishment, providing important insight into the Liddle syndrome defects. ..
  3. Yang L, Rinke R, Korbmacher C. Stimulation of the epithelial sodium channel (ENaC) by cAMP involves putative ERK phosphorylation sites in the C termini of the channel's beta- and gamma-subunit. J Biol Chem. 2006;281:9859-68 pubmed
    ..This defines a novel regulatory pathway likely to be relevant for cAMP-induced stimulation of ENaC in vivo. ..
  4. Michlig S, Harris M, Loffing J, Rossier B, Firsov D. Progesterone down-regulates the open probability of the amiloride-sensitive epithelial sodium channel via a Nedd4-2-dependent mechanism. J Biol Chem. 2005;280:38264-70 pubmed
    ..Upon activation of ERK, the effect of Nedd4-2 on ENaC open probability can become more important than its effect on ENaC cell-surface expression. ..
  5. Shi H, Asher C, Chigaev A, Yung Y, Reuveny E, Seger R, et al. Interactions of beta and gamma ENaC with Nedd4 can be facilitated by an ERK-mediated phosphorylation. J Biol Chem. 2002;277:13539-47 pubmed
    ..It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4. ..
  6. Pradervand S, Wang Q, Burnier M, Beermann F, Horisberger J, Hummler E, et al. A mouse model for Liddle's syndrome. J Am Soc Nephrol. 1999;10:2527-33 pubmed
    ..This animal model reproduces to a large extent a human form of salt-sensitive hypertension and establishes a causal relationship between dietary salt, a gene expressed in kidney and hypertension. ..
  7. Caldwell R, Boucher R, Stutts M. Serine protease activation of near-silent epithelial Na+ channels. Am J Physiol Cell Physiol. 2004;286:C190-4 pubmed
    ..Modulation of ENaC Po by endogenous epithelial serine proteases is a potentially important regulator of epithelial Na+ transport, distinct from the regulation achieved by hormone-induced plasma membrane insertion of channels. ..
  8. Auberson M, Hoffmann Pochon N, Vandewalle A, Kellenberger S, Schild L. Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin. Am J Physiol Renal Physiol. 2003;285:F459-71 pubmed
  9. Canessa C, Schild L, Buell G, Thorens B, Gautschi I, Horisberger J, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994;367:463-7 pubmed
    ..The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel. ..

More Information


  1. Ergonul Z, Frindt G, Palmer L. Regulation of maturation and processing of ENaC subunits in the rat kidney. Am J Physiol Renal Physiol. 2006;291:F683-93 pubmed
    ..Changes in the processing and maturation of the channels occur rapidly enough to be involved in the daily regulation of ENaC activity and Na reabsorption by the kidney. ..
  2. Hitomi Y, Suzuki A, Kawano Y, Nozawa Inoue K, Inoue M, Maeda T. Immunohistochemical detection of ENaCbeta in the terminal Schwann cells associated with the periodontal Ruffini endings of the rat incisor. Biomed Res. 2009;30:113-9 pubmed
    ..These findings suggest that ENaCbeta is a key mechanotransducing channel in the periodontal Ruffini endings. Probably, the terminal Schwann cells together with the axon terminals regulate mechanotransduction in the periodontal endings. ..
  3. Kim S, Wang W, Nielsen J, Praetorius J, Kwon T, Knepper M, et al. Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats. Am J Physiol Renal Physiol. 2004;286:F922-35 pubmed
    ..The decreased abundance of NHE3, BSC-1, TSC, and Na-K-ATPase may play a compensatory role to promote sodium excretion. ..
  4. Rauh R, Hoerner C, Korbmacher C. ???-ENaC is inhibited by CFTR but stimulated by cAMP in Xenopus laevis oocytes. Am J Physiol Lung Cell Mol Physiol. 2017;312:L277-L287 pubmed publisher
  5. Song J, Kwon S, Cho C, Park S, Chae S. Expression of ENaC in LPS-induced inflammation of middle ear mucosa. Acta Otolaryngol. 2012;132:1145-50 pubmed publisher
    ..At 24 h, ENaC-? immunoreactivity was normalized, then at 72 and 120 h after the injection it was increased. ..
  6. Ruete M, Carrizo L, Bocanegra M, Valles P. Altered renal expression of Na(+) transporters and ROMK in protein-deprived rats. Nephron Physiol. 2009;111:p17-29 pubmed publisher
    ..A role of aldosterone may be suggested. ..
  7. Planes C, Blot Chabaud M, Matthay M, Couette S, Uchida T, Clerici C. Hypoxia and beta 2-agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells. J Biol Chem. 2002;277:47318-24 pubmed
  8. Ahn Y, Brooker D, Kosari F, Harte B, Li J, Mackler S, et al. Cloning and functional expression of the mouse epithelial sodium channel. Am J Physiol. 1999;277:F121-9 pubmed
  9. Shimkets R, Warnock D, Bositis C, Nelson Williams C, Hansson J, Schambelan M, et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994;79:407-14 pubmed
    ..These findings demonstrate that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis. ..
  10. Shimkets R, Lifton R, Canessa C. In vivo phosphorylation of the epithelial sodium channel. Proc Natl Acad Sci U S A. 1998;95:3301-5 pubmed
    ..The results suggest that aldosterone, insulin, and protein kinases A and C modulate the activity of ENaC by phosphorylation of the carboxyl termini of the beta and gamma subunits. ..
  11. Inagaki A, Yamaguchi S, Ishikawa T. Amiloride-sensitive epithelial Na+ channel currents in surface cells of rat rectal colon. Am J Physiol Cell Physiol. 2004;286:C380-90 pubmed
  12. Mazzochi C, Bubien J, Smith P, Benos D. The carboxyl terminus of the alpha-subunit of the amiloride-sensitive epithelial sodium channel binds to F-actin. J Biol Chem. 2006;281:6528-38 pubmed
    ..This is the first study to report a direct and specific biochemical interaction between F-actin and ENaC. ..
  13. Hanwell D, Ishikawa T, Saleki R, Rotin D. Trafficking and cell surface stability of the epithelial Na+ channel expressed in epithelial Madin-Darby canine kidney cells. J Biol Chem. 2002;277:9772-9 pubmed
    ..Collectively, these results help elucidate key aspects of ENaC trafficking and turnover rates in mammalian kidney epithelial cells. ..
  14. Nielsen J, Kwon T, Praetorius J, Kim Y, Frøkiaer J, Knepper M, et al. Segment-specific ENaC downregulation in kidney of rats with lithium-induced NDI. Am J Physiol Renal Physiol. 2003;285:F1198-209 pubmed
  15. Coote K, Atherton H, Young A, Sugar R, Burrows R, Smith N, et al. The guinea-pig tracheal potential difference as an in vivo model for the study of epithelial sodium channel function in the airways. Br J Pharmacol. 2008;155:1025-33 pubmed publisher
    ..The guinea-pig TPD therefore represents a suitable in vivo model of human airway epithelial ion transport...
  16. Dagenais A, Frechette R, Yamagata Y, Yamagata T, Carmel J, Clermont M, et al. Downregulation of ENaC activity and expression by TNF-alpha in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2004;286:L301-11 pubmed
    ..All these data show that TNF-alpha, a proinflammatory cytokine present during lung infection, has a profound influence on the capacity of alveolar epithelial cells to transport sodium. ..
  17. Frindt G, Ergonul Z, Palmer L. Surface expression of epithelial Na channel protein in rat kidney. J Gen Physiol. 2008;131:617-27 pubmed publisher
    ..Changes in the surface density of ENaC subunits contribute significantly to the regulation of Na transport in renal cells by mineralocorticoid hormone, but do not fully account for increased channel activity. ..
  18. Wakida N, Kitamura K, Tuyen D, Maekawa A, Miyoshi T, Adachi M, et al. Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-beta1 and aldosterone. Kidney Int. 2006;70:1432-8 pubmed
    ..PN-1 could represent a new factor that contributes to regulation of ENaC activity in the kidney. ..
  19. Li Y, Zhang D, Tu H, Muelleman R. Altered ENaC is Associated With Aortic Baroreceptor Dysfunction in Chronic Heart Failure. Am J Hypertens. 2016;29:582-9 pubmed publisher
    ..Baroreceptors should be a potential therapeutic target for reducing mortality in CHF. ..
  20. Yu Z, Schumacher M, Frey B, Frey F, Vogt B. Regulation of epithelial sodium channel in puromycin aminonucleoside-induced unilateral experimental nephrotic syndrome in normal and analbuminemic Nagase rats. Nephron Physiol. 2005;101:p51-62 pubmed
    ..ENaC mRNA and protein expression are not increased in the early phase of unilateral PAN-induced NS. Sgk1, Nedd4-2 and analbuminemia are not important regulatory factors of ENaC protein expression in experimental NS. ..
  21. Ishikawa T, Jiang C, Stutts M, Marunaka Y, Rotin D. Regulation of the epithelial Na+ channel by cytosolic ATP. J Biol Chem. 2003;278:38276-86 pubmed
    ..We propose that this novel ATP regulation of ENaC may be, at least in part, involved in the fine-tuning of ENaC activity under physiologic and pathophysiologic conditions. ..
  22. Konstas A, Koch J, Korbmacher C. cAMP-dependent activation of CFTR inhibits the epithelial sodium channel (ENaC) without affecting its surface expression. Pflugers Arch. 2003;445:513-21 pubmed
    ..We conclude that the inhibitory effect of cAMP-activated CFTR on ENaC is due to a decrease in channel open probability. ..
  23. Collier D, Snyder P. Extracellular protons regulate human ENaC by modulating Na+ self-inhibition. J Biol Chem. 2009;284:792-8 pubmed publisher
    ..Together, the data support a model in which protons modulate ENaC gating by relieving Na(+) self-inhibition. We speculate that this may be an important mechanism to facilitate epithelial Na(+) transport under conditions of acidosis. ..
  24. Kaufmann S, Westenbroek R, Zechner C, Maass A, Bischoff S, Muck J, et al. Functional protein expression of multiple sodium channel alpha- and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol. 2010;48:261-9 pubmed publisher
    ..Thus, as in the adult heart, a range of sodium channel alpha-subunits are expressed in neonatal myocytes in addition to the predominant TTX-resistant Na(v)1.5 alpha-subunit and they contribute to the total sodium current. ..
  25. Lee I, Dinudom A, Sanchez Perez A, Kumar S, Cook D. Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. J Biol Chem. 2007;282:29866-73 pubmed
    ..Together these data suggest that both Akt and Sgk are components of an insulin signaling pathway that increases Na(+) absorption by up-regulating membrane expression of ENaC via a regulatory system that involves inhibition of Nedd4-2. ..
  26. Hobbs C, Blanchard M, Alijevic O, Tan C, Kellenberger S, Bencharit S, et al. Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures. Am J Physiol Lung Cell Mol Physiol. 2013;305:L990-L1001 pubmed publisher
    ..Furthermore, the robust inhibition of ENaC by the S18 peptide suggests that this peptide may be suitable for treating CF lung disease. ..
  27. Kanelis V, Rotin D, Forman Kay J. Solution structure of a Nedd4 WW domain-ENaC peptide complex. Nat Struct Biol. 2001;8:407-12 pubmed
    ..The Nedd4 WW domain-ENaC betaP2 peptide structure expands our understanding of the mechanisms involved in WW domain-ligand recognition and the molecular basis of Liddle syndrome. ..
  28. Frindt G, Ergonul Z, Palmer L. Na channel expression and activity in the medullary collecting duct of rat kidney. Am J Physiol Renal Physiol. 2007;292:F1190-6 pubmed
    ..These findings suggest that the capability of hormone-regulated, channel-mediated Na reabsorption by the nephron extends at least into the outer medullary collecting duct. ..
  29. Drummond H, Gebremedhin D, Harder D. Degenerin/epithelial Na+ channel proteins: components of a vascular mechanosensor. Hypertension. 2004;44:643-8 pubmed
    ..These data suggest that DEG/ENaC proteins are required for vessel responses to pressure and are consistent with the evolutionary conservation of mechanosensory function of DEG/ENaC proteins. ..
  30. Kienitz T, Allolio B, Strasburger C, Quinkler M. Sex-specific regulation of ENaC and androgen receptor in female rat kidney. Horm Metab Res. 2009;41:356-62 pubmed publisher
    ..Our data demonstrate that AR and ENaC are regulated by sex steroids. That way sex steroids might modulate renal sodium reabsorption and therefore provide a possible explanation for sex differences in blood pressure. ..
  31. Otulakowski G, Rafii B, O Brodovich H. Differential translational efficiency of ENaC subunits during lung development. Am J Respir Cell Mol Biol. 2004;30:862-70 pubmed
    ..We conclude that there are different translational efficiencies for ENaC subunits and that perinatal processes globally modulate lung mRNA translation. ..
  32. Farr T, Coddington Lawson S, Snyder P, McDonald F. Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits. Biochem J. 2000;345 Pt 3:503-9 pubmed
    ..In addition, when co-expressed in Xenopus oocytes, human Nedd4 down-regulates Na(+)-channel activity. ..
  33. Harvey K, Dinudom A, Komwatana P, Jolliffe C, Day M, Parasivam G, et al. All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+. J Biol Chem. 1999;274:12525-30 pubmed
    ..We propose that Nedd4-mediated down-regulation of Na+ channels involves the binding of WW domains 2 and 3 to the Na+ channel and of WW domain 1 to an unknown associated protein. ..
  34. Asher C, Chigaev A, Garty H. Characterization of interactions between Nedd4 and beta and gammaENaC using surface plasmon resonance. Biochem Biophys Res Commun. 2001;286:1228-31 pubmed
    ..These data provides the first determination of association, dissociation and equilibrium constants for the interactions between WW2 and beta or gammaENaC. ..
  35. Jernigan N, LaMarca B, Speed J, Galmiche L, Granger J, Drummond H. Dietary salt enhances benzamil-sensitive component of myogenic constriction in mesenteric arteries. Am J Physiol Heart Circ Physiol. 2008;294:H409-20 pubmed
    ..These data suggest that dietary sodium regulates ENaC expression and the quantitative importance of the vascular ENaC signaling pathway contributing to myogenic constriction. ..
  36. Plettenberg S, Weiss E, Lemor R, Wehner F. Subunits alpha, beta and gamma of the epithelial Na+ channel (ENaC) are functionally related to the hypertonicity-induced cation channel (HICC) in rat hepatocytes. Pflugers Arch. 2008;455:1089-95 pubmed
    ..It is concluded that all three subunits of the ENaC are functionally related to RVI and HICC activation in rat hepatocytes. ..
  37. Falin R, Cotton C. Acute downregulation of ENaC by EGF involves the PY motif and putative ERK phosphorylation site. J Gen Physiol. 2007;130:313-28 pubmed
    ..Our results are consistent with an ERK-mediated decrease in ENaC open probability and enhanced retrieval of sodium channels from the apical membrane. ..
  38. Kanelis V, Farrow N, Kay L, Rotin D, Forman Kay J. NMR studies of tandem WW domains of Nedd4 in complex with a PY motif-containing region of the epithelial sodium channel. Biochem Cell Biol. 1998;76:341-50 pubmed
    ..Data collected on the WW(II+III)-betaP2 complex indicate that these WW domains have different affinities for the betaP2 peptide. ..
  39. Bachhuber T, König J, Voelcker T, Mürle B, Schreiber R, Kunzelmann K. Cl- interference with the epithelial Na+ channel ENaC. J Biol Chem. 2005;280:31587-94 pubmed
    ..The results confirm a role of the carboxyl terminus of betaENaC for Cl(-)-dependent inhibition of the Na+ channel, which, however, may only be part of a complex regulation of ENaC by CFTR. ..
  40. Gille T, Randrianarison Pellan N, Goolaerts A, Dard N, Uzunhan Y, Ferrary E, et al. Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway. Am J Respir Cell Mol Biol. 2014;50:526-37 pubmed publisher
    ..Our data strongly suggest that Nedd4-2-mediated ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport. ..
  41. Abramova T, Smolenskaya S, Antonov E, Redina O, Markel A. [Expression of Catechol-O-Methyltransferase (Comt), Mineralocorticoid Receptor (Mlr), and Epithelial Sodium Channel (ENaC) Genes in Kidneys of Hypertensive ISIAH Rats at Rest and during Response to Stress]. Genetika. 2016;52:206-14 pubmed
  42. Henry P, Kanelis V, O Brien M, Kim B, Gautschi I, Forman Kay J, et al. Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel. J Biol Chem. 2003;278:20019-28 pubmed
    ..Collectively, these results suggest that high affinity of WW domain-PY-motif interactions rather than affiliation with Nedd4-1/Nedd-2 is critical for ENaC suppression by Nedd4 proteins. ..
  43. Machida K, Nonoguchi H, Wakamatsu S, Inoue H, Yosifovska T, Inoue T, et al. Acute regulation of the epithelial sodium channel gene by vasopressin and hyperosmolality. Hypertens Res. 2003;26:629-34 pubmed
    ..Determining the physiological significance of the acute effect of vasopressin in MAL will require further investigations. ..
  44. Kreutz R, Struk B, Rubattu S, Hubner N, Szpirer J, Szpirer C, et al. Role of the alpha-, beta-, and gamma-subunits of epithelial sodium channel in a model of polygenic hypertension. Hypertension. 1997;29:131-6 pubmed
    ..Our results fail to support a material contribution of the epithelial sodium channel genes to blood pressure regulation in this model of polygenic hypertension. ..
  45. Yu Z, Serra A, Sauter D, Loffing J, Ackermann D, Frey F, et al. Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC). Nephrol Dial Transplant. 2005;20:1833-41 pubmed
    ..0005). Enhanced abundance of NCC was observed in the initial stage after BDL, followed by a marked decrease. ENaC transcription, translation or cell surface abundance was not increased after BDL. ..
  46. Teruyama R, Sakuraba M, Wilson L, Wandrey N, Armstrong W. Epithelial Na? sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei. Am J Physiol Endocrinol Metab. 2012;302:E273-85 pubmed publisher
    ..These results strongly suggest the presence of functional ENaCs that may affect the firing patterns of MNCs, which ultimately control the secretion of VP and OT. ..
  47. Kim E, Ahn D, Yeon S, Lim M, Lee Y. Epithelial Na+ channel proteins are mechanotransducers of myogenic constriction in rat posterior cerebral arteries. Exp Physiol. 2012;97:544-55 pubmed publisher
    ..Our results suggest that ENaCs may play an important role as mechanosensitive ion channels initiating pressure-induced myogenic responses in rat PCA. ..
  48. Warrington J, Coleman K, Skaggs C, Hosick P, George E, Stec D, et al. Heme oxygenase-1 promotes migration and ?-epithelial Na+ channel expression in cytotrophoblasts and ischemic placentas. Am J Physiol Regul Integr Comp Physiol. 2014;306:R641-6 pubmed publisher
    ..HO-1 regulation of cytotrophoblast ?-ENaC expression and migration may be a potential therapeutic target in preeclamptic patients. ..
  49. Zhong S, Liu Z. Immunohistochemical localization of the epithelial sodium channel in the rat inner ear. Hear Res. 2004;193:1-8 pubmed
    ..In conclusion, our results suggest that functional ENaC in the labyrinth may work in concert with other Na+ and K+ transport molecules to regulate endolymph and to maintain homeostasis in the inner ear. ..
  50. Amin M, Reza E, El Shahat E, Wang H, Tesson F, Leenen F. Enhanced expression of epithelial sodium channels in the renal medulla of Dahl S rats. Can J Physiol Pharmacol. 2011;89:159-68 pubmed publisher
    ..R rats on regular salt, and further increased on high salt. The persistent high expression of ?ENaC and increase in apical localization of ? and ?ENaC may contribute to greater retention of sodium in S rats on a high-salt diet. ..
  51. Chang S, Grunder S, Hanukoglu A, Rosler A, Mathew P, Hanukoglu I, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996;12:248-53 pubmed
    ..These findings demonstrate the molecular basis and explain the pathophysiology of this disease. ..
  52. Grifoni S, Gannon K, Stec D, Drummond H. ENaC proteins contribute to VSMC migration. Am J Physiol Heart Circ Physiol. 2006;291:H3076-86 pubmed
    ..These data indicate that expression of ENaC proteins is required for normal VSMC migration and suggest a potential new role for ENaC proteins in vascular tissue repair. ..
  53. Xie Y, Schafer J. Inhibition of ENaC by intracellular Cl- in an MDCK clone with high ENaC expression. Am J Physiol Renal Physiol. 2004;287:F722-31 pubmed
    ..91 +/- 0.16 to 1.32 +/- 0.17 fmol/cm2 and in the intrinsic channel activity (the average current per ENaC subunit) from 13.3 +/- 1.2 to 8.2 +/- 1.4 microA/fmol. ..