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  1. Article ; Online: The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC): IUPHAR Review 19.

    Boscardin, Emilie / Alijevic, Omar / Hummler, Edith / Frateschi, Simona / Kellenberger, Stephan

    British journal of pharmacology

    2016  Volume 173, Issue 18, Page(s) 2671–2701

    Abstract: Acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC) are both members of the ENaC/degenerin family of amiloride-sensitive Na(+) channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, ... ...

    Abstract Acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC) are both members of the ENaC/degenerin family of amiloride-sensitive Na(+) channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, to fear behaviour, learning and pain sensation. ENaC mediates Na(+) reabsorption across epithelia of the distal kidney and colon and of the airways. ENaC is a clinically used drug target in the context of hypertension and cystic fibrosis, while ASIC is an interesting potential target. Following a brief introduction, here we will review selected aspects of ASIC and ENaC function. We discuss the origin and nature of pH changes in the brain and the involvement of ASICs in synaptic signalling. We expose how in the peripheral nervous system, ASICs cover together with other ion channels a wide pH range as proton sensors. We introduce the mechanisms of aldosterone-dependent ENaC regulation and the evidence for an aldosterone-independent control of ENaC activity, such as regulation by dietary K(+) . We then provide an overview of the regulation of ENaC by proteases, a topic of increasing interest over the past few years. In spite of the profound differences in the physiological and pathological roles of ASICs and ENaC, these channels share many basic functional and structural properties. It is likely that further research will identify physiological contexts in which ASICs and ENaC have similar or overlapping roles.
    MeSH term(s) Acid Sensing Ion Channels/metabolism ; Animals ; Epithelial Sodium Channels/metabolism ; Humans ; Hydrogen-Ion Concentration
    Chemical Substances Acid Sensing Ion Channels ; Epithelial Sodium Channels
    Language English
    Publishing date 2016-08-10
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.13533
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interaction between Epithelial Sodium Channel

    Sassi, Ali / Wang, Yubao / Chassot, Alexandra / Komarynets, Olga / Roth, Isabelle / Olivier, Valérie / Crambert, Gilles / Dizin, Eva / Boscardin, Emilie / Hummler, Edith / Feraille, Eric

    Journal of the American Society of Nephrology : JASN

    2020  Volume 31, Issue 5, Page(s) 1009–1023

    Abstract: Background: Water and solute transport across epithelia can occur : Methods: To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability : Results: Overexpression or silencing of the ENaC ...

    Abstract Background: Water and solute transport across epithelia can occur
    Methods: To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability
    Results: Overexpression or silencing of the ENaC
    Conclusions: Our data reveal the specific coupling between ENaC
    MeSH term(s) Amiloride/analogs & derivatives ; Amiloride/pharmacology ; Animals ; Biological Transport ; Cells, Cultured ; Chlorides/metabolism ; Claudins/deficiency ; Claudins/genetics ; Claudins/metabolism ; Epithelial Sodium Channels/deficiency ; Epithelial Sodium Channels/genetics ; Epithelial Sodium Channels/metabolism ; Gene Expression Regulation ; Gene Silencing ; Ion Transport ; Kidney Tubules, Collecting/metabolism ; Mice ; Mice, Knockout ; RNA, Messenger/biosynthesis ; Recombinant Proteins/metabolism ; Sodium/metabolism ; Transduction, Genetic
    Chemical Substances Chlorides ; Claudins ; Epithelial Sodium Channels ; RNA, Messenger ; Recombinant Proteins ; Scnn1g protein, mouse ; benzamil (04659UUJ94) ; Amiloride (7DZO8EB0Z3) ; Sodium (9NEZ333N27) ; claudin 8 (HJ6C19SU7L)
    Language English
    Publishing date 2020-04-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2019080790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Regulation of blood pressure and renal function by NCC and ENaC: lessons from genetically engineered mice.

    Verouti, Sophia N / Boscardin, Emilie / Hummler, Edith / Frateschi, Simona

    Current opinion in pharmacology

    2015  Volume 21, Page(s) 60–72

    Abstract: The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) ...

    Abstract The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late DCT and in the cortical collecting ducts (CCD) providing the final renal adjustment to Na(+) balance. Here, we aim to highlight the recent advances made using transgenic mouse models towards the understanding of the regulation of NCC and ENaC function relevant to the control of sodium balance and blood pressure. We thus like to pave the way for common mechanisms regulating these two sodium-transporting proteins and their potential implication in structural remodeling of the nephron segments and Na(+) and Cl(-) reabsorption.
    MeSH term(s) Animals ; Blood Pressure/physiology ; Epithelial Sodium Channels/physiology ; Humans ; Insulin/physiology ; Kidney/physiology ; Mice, Transgenic ; Minor Histocompatibility Antigens ; Protein-Serine-Threonine Kinases/physiology ; Renin-Angiotensin System/physiology ; Solute Carrier Family 12, Member 3/physiology ; Vasopressins/physiology ; WNK Lysine-Deficient Protein Kinase 1
    Chemical Substances Epithelial Sodium Channels ; Insulin ; Minor Histocompatibility Antigens ; Slc12a3 protein, mouse ; Solute Carrier Family 12, Member 3 ; Vasopressins (11000-17-2) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; WNK Lysine-Deficient Protein Kinase 1 (EC 2.7.11.1) ; Wnk1 protein, mouse (EC 2.7.11.1)
    Language English
    Publishing date 2015-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2037057-X
    ISSN 1471-4973 ; 1471-4892
    ISSN (online) 1471-4973
    ISSN 1471-4892
    DOI 10.1016/j.coph.2014.12.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific

    Boscardin, Emilie / Perrier, Romain / Sergi, Chloé / Maillard, Marc P / Loffing, Johannes / Loffing-Cueni, Dominique / Koesters, Robert / Rossier, Bernard C / Hummler, Edith

    Journal of the American Society of Nephrology : JASN

    2018  Volume 29, Issue 3, Page(s) 977–990

    Abstract: The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of ... ...

    Abstract The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the
    MeSH term(s) Animals ; Chelating Agents/therapeutic use ; Dietary Supplements ; Epithelial Sodium Channels/genetics ; Hyperkalemia/blood ; Hyperkalemia/drug therapy ; Hyperkalemia/genetics ; Mice ; Mice, Knockout ; Nephrons ; Polystyrenes/therapeutic use ; Potassium/blood ; Potassium, Dietary/administration & dosage ; Pseudohypoaldosteronism/blood ; Pseudohypoaldosteronism/genetics ; Sodium, Dietary/administration & dosage ; Solute Carrier Family 12, Member 3/metabolism
    Chemical Substances Chelating Agents ; Epithelial Sodium Channels ; Polystyrenes ; Potassium, Dietary ; Scnn1b protein, mouse ; Scnn1g protein, mouse ; Slc12a3 protein, mouse ; Sodium, Dietary ; Solute Carrier Family 12, Member 3 ; polystyrene sulfonic acid (70KO0R01RY) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2018-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2017030345
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Severe hyperkalemia is rescued by low-potassium diet in renal βENaC-deficient mice.

    Boscardin, Emilie / Perrier, Romain / Sergi, Chloé / Maillard, Marc / Loffing, Johannes / Loffing-Cueni, Dominique / Koesters, Robert / Rossier, Bernard Claude / Hummler, Edith

    Pflugers Archiv : European journal of physiology

    2017  Volume 469, Issue 10, Page(s) 1387–1399

    Abstract: In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium ( ... ...

    Abstract In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa
    MeSH term(s) Animals ; Diet, Sodium-Restricted ; Epithelial Sodium Channels/metabolism ; Hyperkalemia/metabolism ; Kidney/metabolism ; Mice, Transgenic ; Nephrons/metabolism ; Phenotype ; Potassium/metabolism ; Potassium Channels, Inwardly Rectifying/metabolism ; Sodium/metabolism
    Chemical Substances Epithelial Sodium Channels ; Potassium Channels, Inwardly Rectifying ; Sodium (9NEZ333N27) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2017-05-31
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-017-1990-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Lack of Renal Tubular Glucocorticoid Receptor Decreases the Thiazide-Sensitive Na

    Canonica, Jérémie / Frateschi, Simona / Boscardin, Emilie / Ebering, Anna / Sergi, Chloé / Jäger, Yannick / Peyrollaz, Thibaud / Mérillat, Anne-Marie / Maillard, Marc / Klusonova, Petra / Odermatt, Alex / Koesters, Robert / Debonneville, Anne / Staub, Olivier / Verouti, Sophia N / Hummler, Edith

    Frontiers in physiology

    2019  Volume 10, Page(s) 989

    Abstract: Chronic glucocorticoid infusion impairs NCC activity and induces a non-dipping profile in mice, suggesting that glucocorticoids are essential for daily blood pressure variations. In this paper, we studied mice lacking the renal tubular glucocorticoid ... ...

    Abstract Chronic glucocorticoid infusion impairs NCC activity and induces a non-dipping profile in mice, suggesting that glucocorticoids are essential for daily blood pressure variations. In this paper, we studied mice lacking the renal tubular glucocorticoid receptor (GR) in adulthood (GR knockouts,
    Language English
    Publishing date 2019-08-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2019.00989
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Severe Salt-Losing Syndrome and Hyperkalemia Induced by Adult Nephron-Specific Knockout of the Epithelial Sodium Channel α-Subunit.

    Perrier, Romain / Boscardin, Emilie / Malsure, Sumedha / Sergi, Chloé / Maillard, Marc P / Loffing, Johannes / Loffing-Cueni, Dominique / Sørensen, Mads Vaarby / Koesters, Robert / Rossier, Bernard C / Frateschi, Simona / Hummler, Edith

    Journal of the American Society of Nephrology : JASN

    2015  Volume 27, Issue 8, Page(s) 2309–2318

    Abstract: Systemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt-losing syndrome caused by loss-of-function mutations of the amiloride-sensitive epithelial sodium channel (ENaC) and characterized by neonatal life-threatening hypovolemia and hyperkalemia. ...

    Abstract Systemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt-losing syndrome caused by loss-of-function mutations of the amiloride-sensitive epithelial sodium channel (ENaC) and characterized by neonatal life-threatening hypovolemia and hyperkalemia. The very high plasma aldosterone levels detected under hypovolemic or hyperkalemic challenge can lead to increased or decreased sodium reabsorption, respectively, through the Na(+)/Cl(-) cotransporter (NCC). However, the role of ENaC deficiency remains incompletely defined, because constitutive inactivation of individual ENaC subunits is neonatally lethal in mice. We generated adult inducible nephron-specific αENaC-knockout mice (Scnn1a(Pax8/LC1)) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1. Compared with control mice fed a regular-salt diet, knockout mice fed a regular-salt diet exhibited downregulated expression and phosphorylation of NCC protein, despite high plasma aldosterone levels. In knockout mice fed a high-sodium and reduced-potassium diet (rescue diet), although plasma aldosterone levels remained significantly increased, NCC expression returned to control levels, and body weight, plasma and urinary electrolyte concentrations, and excretion normalized. Finally, shift to a regular diet after the rescue diet reinstated the symptoms of severe PHA-1 syndrome and significantly reduced NCC phosphorylation. In conclusion, lack of ENaC-mediated sodium transport along the nephron cannot be compensated for by other sodium channels and/or transporters, only by a high-sodium and reduced-potassium diet. We further conclude that hyperkalemia becomes the determining factor in regulating NCC activity, regardless of sodium loss, in the ENaC-mediated salt-losing PHA-1 phenotype.
    MeSH term(s) Animals ; Epithelial Sodium Channels/genetics ; Hyperkalemia/genetics ; Mice ; Mice, Knockout ; Nephrons ; Pseudohypoaldosteronism/genetics ; Severity of Illness Index
    Chemical Substances Epithelial Sodium Channels
    Language English
    Publishing date 2015-12-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2015020154
    Database MEDical Literature Analysis and Retrieval System OnLINE

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