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Regulated sodium transport in the renal connecting tubule (CNT) via the epithelial sodium channel (ENaC)

  • Ion Channels, Receptors and Transporters
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The aldosterone-sensitive distal nephron (ASDN) includes the late distal convoluted tubule 2, the connecting tubule (CNT) and the collecting duct. The appropriate regulation of sodium (Na+) absorption in the ASDN is essential to precisely match urinary Na+ excretion to dietary Na+ intake whilst taking extra-renal Na+ losses into account. There is increasing evidence that Na+ transport in the CNT is of particular importance for the maintenance of body Na+ balance and for the long-term control of extra-cellular fluid volume and arterial blood pressure. Na+ transport in the CNT critically depends on the activity and abundance of the amiloride-sensitive epithelial sodium channel (ENaC) in the luminal membrane of the CNT cells. As a rate-limiting step for transepithelial Na+ transport, ENaC is the main target of hormones (e.g. aldosterone, angiotensin II, vasopressin and insulin/insulin-like growth factor 1) to adjust transepithelial Na+ transport in this tubular segment. In this review, we highlight the structural and functional properties of the CNT that contribute to the high Na+ transport capacity of this segment. Moreover, we discuss some aspects of the complex pathways and molecular mechanisms involved in ENaC regulation by hormones, kinases, proteases and associated proteins that control its function. Whilst cultured cells and heterologous expression systems have greatly advanced our knowledge about some of these regulatory mechanisms, future studies will have to determine the relative importance of the various pathways in the native tubule and in particular in the CNT.

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References

  1. Abriel H, Loffing J, Rebhun JF, Pratt JH, Schild L, Horisberger JD, Rotin D, Staub O (1999) Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle’s syndrome. J Clin Invest 103:667–673

    PubMed  CAS  Google Scholar 

  2. Adachi M, Kitamura K, Miyoshi T, Narikiyo T, Iwashita K, Shiraishi N, Nonoguchi H, Tomita K (2001) Activation of epithelial sodium channels by prostasin in Xenopus oocytes. J Am Soc Nephrol 12:1114–1121

    PubMed  CAS  Google Scholar 

  3. Adebamiro A, Cheng Y, Rao US, Danahay H, Bridges RJ (2007) A segment of γENaC mediates elastase activation of Na+ transport. J Gen Physiol 130:611–629

    PubMed  CAS  Google Scholar 

  4. Almeida AJ, Burg MB (1982) Sodium transport in the rabbit connecting tubule. Am J Physiol 243:F330–F334

    PubMed  CAS  Google Scholar 

  5. Alvarez de la Rosa D, Zhang P, Naray Fejes Toth A, Fejes Toth G, Canessa CM (1999) The serum and glucocorticoid kinase sgk increases the abundance of epithelial sodium channels in the plasma membrane of Xenopus oocytes. J Biol Chem 274:37834–37839

    PubMed  CAS  Google Scholar 

  6. Alvarez de la Rosa D, Coric T, Todorovic N, Shao D, Wang T, Canessa CM (2003) Distribution and regulation of expression of serum- and glucocorticoid-induced kinase-1 in the rat kidney. J Physiol 551:455–466

    PubMed  CAS  Google Scholar 

  7. Anantharam A, Tian Y, Palmer LG (2006) Open probability of the epithelial sodium channel is regulated by intracellular sodium. J Physiol 574:333–347

    PubMed  CAS  Google Scholar 

  8. Anantharam A, Palmer LG (2007) Determination of epithelial Na+ channel subunit stoichiometry from single-channel conductances. J Gen Physiol 130:55–70

    PubMed  CAS  Google Scholar 

  9. Andreasen D, Vuagniaux G, Fowler-Jaeger N, Hummler E, Rossier BC (2006) Activation of epithelial sodium channels by mouse channel activating proteases (mCAP) expressed in Xenopus oocytes requires catalytic activity of mCAP3 and mCAP2 but not mCAP1. J Am Soc Nephrol 17:968–976

    PubMed  CAS  Google Scholar 

  10. Araki N, Umemura M, Miyagi Y, Yabana M, Miki Y, Tamura K, Uchino K, Aoki R, Goshima Y, Umemura S, Ishigami T (2008) Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant: implications for essential hypertension. Hypertension 51:773–777

    PubMed  CAS  Google Scholar 

  11. Arteaga MF, Canessa CM (2005) Functional specificity of Sgk1 and Akt1 on ENaC activity. Am J Physiol Renal Physiol 289:F90–F96

    PubMed  CAS  Google Scholar 

  12. Auberson M, Hoffmann-Pochon N, Vandewalle A, Kellenberger S, Schild L (2003) Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin. Am J Physiol Renal Physiol 285:F459–F471

    PubMed  Google Scholar 

  13. Awayda MS, Shao W, Guo F, Zeidel M, Hill WG (2004) ENaC-membrane interactions: regulation of channel activity by membrane order. J Gen Physiol 123:709–727

    PubMed  CAS  Google Scholar 

  14. Bachmann S, Bostanjoglo M, Schmitt R, Ellison DH (1999) Sodium transport-related proteins in the mammalian distal nephron—distribution, ontogeny and functional aspects. Anat Embryol (Berl) 200:447–468

    CAS  Google Scholar 

  15. Balut C, Steels P, Radu M, Ameloot M, Driessche WV, Jans D (2006) Membrane cholesterol extraction decreases Na+ transport in A6 renal epithelia. Am J Physiol Cell Physiol 290:C87–C94

    PubMed  CAS  Google Scholar 

  16. Bankir L, Fernandes S, Bardoux P, Bouby N, Bichet DG (2005) Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans. J Am Soc Nephrol 16:1920–1928

    PubMed  CAS  Google Scholar 

  17. Barajas L, Powers K, Carretero O, Scicli AG, Inagami T (1986) Immunocytochemical localization of renin and kallikrein in the rat renal cortex. Kidney Int 29:965–970

    PubMed  CAS  Google Scholar 

  18. Baxendale-Cox LM, Duncan RL (1999) Insulin increases sodium (Na+) channel density in A6 epithelia: implications for expression of hypertension. Biol Res Nurs 1:20–29

    PubMed  CAS  Google Scholar 

  19. Bengrine A, Li J, Hamm LL, Awayda MS (2007) Indirect activation of the epithelial Na+ channel by trypsin. J Biol Chem 282:26884–26896

    PubMed  CAS  Google Scholar 

  20. Bens M, Chassin C, Vandewalle A (2006) Regulation of NaCl transport in the renal collecting duct: lessons from cultured cells. Pflugers Arch 453:133–146

    PubMed  CAS  Google Scholar 

  21. Berdiev BK, Qadri YJ, Benos DJ (2009) Assessment of the CFTR and ENaC association. Mol Biosyst 5:123–127

    PubMed  CAS  Google Scholar 

  22. Bertog M, Cuffe JE, Pradervand S, Hummler E, Hartner A, Porst M, Hilgers KF, Rossier BC, Korbmacher C (2008) Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome. J Physiol 586:459–475

    PubMed  CAS  Google Scholar 

  23. Beutler KT, Masilamani S, Turban S, Nielsen J, Brooks HL, Ageloff S, Fenton RA, Packer RK, Knepper MA (2003) Long-term regulation of ENaC expression in kidney by angiotensin II. Hypertension 41:1143–1150

    PubMed  CAS  Google Scholar 

  24. Bhalla V, Daidie D, Li H, Pao AC, LaGrange LP, Wang J, Vandewalle A, Stockand JD, Staub O, Pearce D (2005) Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4–2 by inducing interaction with 14-3-3. Mol Endocrinol 19:3073–3084

    PubMed  CAS  Google Scholar 

  25. Bhalla V, Oyster NM, Fitch AC, Wijngaarden MA, Neumann D, Schlattner U, Pearce D, Hallows KR (2006) AMP-activated kinase inhibits the epithelial Na+ channel through functional regulation of the ubiquitin ligase Nedd4–2. J Biol Chem 281:26159–26169

    PubMed  CAS  Google Scholar 

  26. Bhalla V, Soundararajan R, Pao AC, Li H, Pearce D (2006) Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ. Am J Physiol Renal Physiol 291:F714–F721

    PubMed  CAS  Google Scholar 

  27. Bhalla V, Hallows KR (2008) Mechanisms of ENaC regulation and clinical implications. J Am Soc Nephrol 19:1845–1854

    PubMed  CAS  Google Scholar 

  28. Bickel CA, Verbalis JG, Knepper MA, Ecelbarger CA (2001) Increased renal Na-K-ATPase, NCC, and β-ENaC abundance in obese Zucker rats. Am J Physiol Renal Physiol 281:F639–F648

    PubMed  CAS  Google Scholar 

  29. Bickel CA, Knepper MA, Verbalis JG, Ecelbarger CA (2002) Dysregulation of renal salt and water transport proteins in diabetic Zucker rats. Kidney Int 61:2099–2110

    PubMed  CAS  Google Scholar 

  30. Biner HL, Arpin-Bott MP, Loffing J, Wang X, Knepper M, Hebert SC, Kaissling B (2002) Human cortical distal nephron: distribution of electrolyte and water transport pathways. J Am Soc Nephrol 13:836–847

    PubMed  Google Scholar 

  31. Bize V, Horisberger JD (2007) Sodium self-inhibition of human epithelial sodium channel: selectivity and affinity of the extracellular sodium sensing site. Am J Physiol 293:F1137–F1146

    Article  CAS  Google Scholar 

  32. Blazer-Yost BL, Cox M, Furlanetto R (1989) Insulin and IGF I receptor-mediated Na+ transport in toad urinary bladders. Am J Physiol 257:C612–C620

    PubMed  CAS  Google Scholar 

  33. Blazer-Yost BL, Liu X, Helman SI (1998) Hormonal regulation of ENaCs: insulin and aldosterone. Am J Physiol 274:C1373–C1379

    PubMed  CAS  Google Scholar 

  34. Blazer-Yost BL, Esterman MA, Vlahos CJ (2003) Insulin-stimulated trafficking of ENaC in renal cells requires PI 3-kinase activity. Am J Physiol Cell Physiol 284:C1645–C1653

    PubMed  CAS  Google Scholar 

  35. Blazer-Yost BL, Vahle JC, Byars JM, Bacallao RL (2004) Real-time three-dimensional imaging of lipid signal transduction: apical membrane insertion of epithelial Na+ channels. Am J Physiol Cell Physiol 287:C1569–C1576

    PubMed  CAS  Google Scholar 

  36. Bondanelli M, Ambrosio MR, degli Uberti EC (2001) Pathogenesis and prevalence of hypertension in acromegaly. Pituitary 4:239–249

    PubMed  CAS  Google Scholar 

  37. Boros S, Bindels RJ, Hoenderop JG (2008) Active Ca2+ reabsorption in the connecting tubule. Pflugers Arch (in press)

  38. Bos JL (2003) Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4:733–738

    PubMed  CAS  Google Scholar 

  39. Bostanjoglo M, Reeves WB, Reilly RF, Velazquez H, Robertson N, Litwack G, Morsing P, Dorup J, Bachmann S, Ellison DH (1998) 11Beta-hydroxysteroid dehydrogenase, mineralocorticoid receptor, and thiazide-sensitive Na-Cl cotransporter expression by distal tubules. J Am Soc Nephrol 9:1347–1358

    PubMed  CAS  Google Scholar 

  40. Boucher RC (2007) Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med 58:157–170

    PubMed  CAS  Google Scholar 

  41. Boulkroun S, Ruffieux-Daidie D, Vitagliano JJ, Poirot O, Charles RP, Lagnaz D, Firsov D, Kellenberger S, Staub O (2008) Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3. Am J Physiol Renal Physiol 295:F889–F900

    PubMed  CAS  Google Scholar 

  42. Brooks HL, Allred AJ, Beutler KT, Coffman TM, Knepper MA (2002) Targeted proteomic profiling of renal Na+ transporter and channel abundances in angiotensin II type 1a receptor knockout mice. Hypertension 39:470–473

    PubMed  CAS  Google Scholar 

  43. Bruns JB, Carattino MD, Sheng S, Maarouf AB, Weisz OA, Pilewski JM, Hughey RP, Kleyman TR (2007) Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit. J Biol Chem 282:6153–6160

    PubMed  CAS  Google Scholar 

  44. Butterworth MB, Edinger RS, Johnson JP, Frizzell RA (2005) Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool. J Gen Physiol 125:81–101

    PubMed  CAS  Google Scholar 

  45. Butterworth MB, Frizzell RA, Johnson JP, Peters KW, Edinger RS (2005) PKA-dependent ENaC trafficking requires the SNARE-binding protein complexin. Am J Physiol Renal Physiol 289:F969–F977

    PubMed  CAS  Google Scholar 

  46. Butterworth MB, Edinger RS, Ovaa H, Burg D, Johnson JP, Frizzell RA (2007) The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel. J Biol Chem 282:37885–37893

    PubMed  CAS  Google Scholar 

  47. Butterworth MB, Edinger RS, Frizzell RA, Johnson JP (2009) Regulation of the epithelial sodium channel by membrane trafficking. Am J Physiol Renal Physiol 296:F10–F24

    PubMed  CAS  Google Scholar 

  48. Caldwell RA, Boucher RC, Stutts MJ (2004) Serine protease activation of near-silent epithelial Na+ channels. Am J Physiol Cell Physiol 286:C190–C194

    PubMed  CAS  Google Scholar 

  49. Caldwell RA, Boucher RC, Stutts MJ (2005) Neutrophil elastase activates near-silent epithelial Na+-channels and increases airway epithelial Na+-transport. Am J Physiol 288:L813–L819

    CAS  Google Scholar 

  50. Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD, Rossier BC (1994) Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 367:463–467

    PubMed  CAS  Google Scholar 

  51. Canessa CM (2007) Structural biology: unexpected opening. Nature 449:293–294

    PubMed  CAS  Google Scholar 

  52. Carattino MD, Edinger RS, Grieser HJ, Wise R, Neumann D, Schlattner U, Johnson JP, Kleyman TR, Hallows KR (2005) Epithelial sodium channel inhibition by AMP-activated protein kinase in oocytes and polarized renal epithelial cells. J Biol Chem 280:17608–17616

    PubMed  CAS  Google Scholar 

  53. Carattino MD, Sheng S, Bruns JB, Pilewski JM, Hughey RP, Kleyman TR (2006) The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit. J Biol Chem 281:18901–18907

    PubMed  CAS  Google Scholar 

  54. Carattino MD, Hughey RP, Kleyman TR (2008) Proteolytic processing of the epithelial sodium channel γ subunit has a dominant role in channel activation. J Biol Chem 283:25290–25295

    PubMed  CAS  Google Scholar 

  55. Carattino MD, Passero CJ, Steren CA, Maarouf AB, Pilewski JM, Myerburg MM, Hughey RP, Kleyman TR (2008) Defining an inhibitory domain in the α-subunit of the epithelial sodium channel. Am J Physiol Renal Physiol 294:F47–F52

    PubMed  CAS  Google Scholar 

  56. Chabot H, Vives MF, Dagenais A, Grygorczyk C, Berthiaume Y, Grygorczyk R (1999) Downregulation of epithelial sodium channel (ENaC) by CFTR co-expressed in Xenopus oocytes is independent of Cl− conductance. J Membr Biol 169:175–188

    PubMed  CAS  Google Scholar 

  57. Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, Firestone GL, Verrey F, Pearce D (1999) Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci U S A 96:2514–2519

    PubMed  CAS  Google Scholar 

  58. Chigaev A, Lu G, Shi H, Asher C, Xu R, Latter H, Seger R, Garty H, Reuveny E (2001) In vitro phosphorylation of COOH termini of the epithelial Na+ channel and its effects on channel activity in Xenopus oocytes. Am J Physiol 280:F1030–F1036

    CAS  Google Scholar 

  59. Chraibi A, Vallet V, Firsov D, Hess SK, Horisberger JD (1998) Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes. J Gen Physiol 111:127–138

    PubMed  CAS  Google Scholar 

  60. Chraibi A, Horisberger JD (2002) Na self inhibition of human epithelial Na channel: temperature dependence and effect of extracellular proteases. J Gen Physiol 120:133–145

    PubMed  CAS  Google Scholar 

  61. Condliffe SB, Carattino MD, Frizzell RA, Zhang H (2003) Syntaxin 1A regulates ENaC via domain-specific interactions. J Biol Chem 278:12796–12804

    PubMed  CAS  Google Scholar 

  62. Coscoy S, Lingueglia E, Lazdunski M, Barbry P (1998) The Phe-Met-Arg-Phe-amide-activated sodium channel is a tetramer. J Biol Chem 273:8317–8322

    PubMed  CAS  Google Scholar 

  63. Costanzo LS (1984) Comparison of calcium and sodium transport in early and late rat distal tubules: effect of amiloride. Am J Physiol 246:F937–F945

    PubMed  CAS  Google Scholar 

  64. Crawford I, Maloney PC, Zeitlin PL, Guggino WB, Hyde SC, Turley H, Gatter KC, Harris A, Higgins CF (1991) Immunocytochemical localization of the cystic fibrosis gene product CFTR. Proc Natl Acad Sci U S A 88:9262–9266

    PubMed  CAS  Google Scholar 

  65. Cuffe JE, Bielfeld-Ackermann A, Thomas J, Leipziger J, Korbmacher C (2000) ATP stimulates Cl− secretion and reduces amiloride-sensitive Na+ absorption in M-1 mouse cortical collecting duct cells. J Physiol 524(Pt 1):77–90

    PubMed  CAS  Google Scholar 

  66. Dahlberg J, Nilsson LO, von Wowern F, Melander O (2007) Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP. PLoS ONE 2:e432

    PubMed  Google Scholar 

  67. Dahlmann A, Pradervand S, Hummler E, Rossier BC, Frindt G, Palmer LG (2003) Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome. Am J Physiol 285:F310–F318

    CAS  Google Scholar 

  68. Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA (2001) Magnesium transport in the renal distal convoluted tubule. Physiol Rev 81:51–84

    PubMed  CAS  Google Scholar 

  69. de Seigneux S, Kim SW, Hemmingsen SC, Frokiaer J, Nielsen S (2006) Increased expression but not targeting of ENaC in adrenalectomized rats with PAN-induced nephrotic syndrome. Am J Physiol Renal Physiol 291:F208–F217

    PubMed  Google Scholar 

  70. Debonneville C, Flores SY, Kamynina E, Plant PJ, Tauxe C, Thomas MA, Münster C, Chraibi A, Pratt JH, Horisberger J-D, Pearce D, Loffing J, Staub O (2001) Phosphorylation of Nedd-4–2 by Sgk1 regulates epithelial Na+ channel cell surface expression. EMBO J 20:7052–7059

    PubMed  CAS  Google Scholar 

  71. DeFronzo RA (1981) The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21:165–171

    PubMed  CAS  Google Scholar 

  72. Deschenes G, Wittner M, Stefano A, Jounier S, Doucet A (2001) Collecting duct is a site of sodium retention in PAN nephrosis: a rationale for amiloride therapy. J Am Soc Nephrol 12:598–601

    PubMed  CAS  Google Scholar 

  73. Devuyst O, Burrow CR, Schwiebert EM, Guggino WB, Wilson PD (1996) Developmental regulation of CFTR expression during human nephrogenesis. Am J Physiol 271:F723–F735

    PubMed  CAS  Google Scholar 

  74. Diakov A, Korbmacher C (2004) A novel pathway of epithelial sodium channel activation involves a serum- and glucocorticoid-inducible kinase consensus motif in the C terminus of the channel’s α-subunit. J Biol Chem 279:38134–38142

    PubMed  CAS  Google Scholar 

  75. Diakov A, Bera K, Mokrushina M, Krueger B, Korbmacher C (2008) Cleavage in the γ-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels. J Physiol 586:4587–4608

    PubMed  CAS  Google Scholar 

  76. Dijkink L, Hartog A, Deen PM, van Os CH, Bindels RJ (1999) Time-dependent regulation by aldosterone of the amiloride-sensitive Na+ channel in rabbit kidney. Pflugers Arch 438:354–360

    PubMed  CAS  Google Scholar 

  77. Dijkink L, Hartog A, van Os CH, Bindels RJ (2002) The epithelial sodium channel (ENaC) is intracellularly located as a tetramer. Pflugers Arch 444:549–555

    PubMed  CAS  Google Scholar 

  78. Dinudom A, Fotia AB, Lefkowitz RJ, Young JA, Kumar S, Cook DI (2004) The kinase Grk2 regulates Nedd4/Nedd4–2-dependent control of epithelial Na+ channels. Proc Natl Acad Sci U S A 101:11886–11890

    PubMed  CAS  Google Scholar 

  79. Djelidi S, Fay M, Cluzeaud F, Escoubet B, Eugene E, Capurro C, Bonvalet JP, Farman N, Blot-Chabaud M (1997) Transcriptional regulation of sodium transport by vasopressin in renal cells. J Biol Chem 272:32919–32924

    PubMed  CAS  Google Scholar 

  80. Donaldson SH, Boucher RC (2007) Sodium channels and cystic fibrosis. Chest 132:1631–1636

    PubMed  CAS  Google Scholar 

  81. Dorup J (1985) Ultrastructure of distal nephron cells in rat renal cortex. J Ultrastruct Res 92:101–118

    PubMed  CAS  Google Scholar 

  82. Dorup J (1988) Ultrastructure of three-dimensionally localized distal nephron segments in superficial cortex of the rat kidney. J Ultrastruct Mol Struct Res 99:169–187

    PubMed  CAS  Google Scholar 

  83. Dorup J, Morsing P, Rasch R (1992) Tubule-tubule and tubule-arteriole contacts in rat kidney distal nephrons. A morphologic study based on computer-assisted three-dimensional reconstructions. Lab Invest 67:761–769

    PubMed  CAS  Google Scholar 

  84. Doucet A, Katz AI (1981) Mineralcorticoid receptors along the nephron: [3H]aldosterone binding in rabbit tubules. Am J Physiol 241:F605–F611

    PubMed  CAS  Google Scholar 

  85. Dupont J, LeRoith D (2001) Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res 55(Suppl 2):22–26

    PubMed  CAS  Google Scholar 

  86. Ecelbarger CA, Kim GH, Terris J, Masilamani S, Mitchell C, Reyes I, Verbalis JG, Knepper MA (2000) Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney. Am J Physiol Renal Physiol 279:F46–F53

    PubMed  CAS  Google Scholar 

  87. Ecelbarger CA, Tiwari S (2006) Sodium transporters in the distal nephron and disease implications. Curr Hypertens Rep 8:158–165

    PubMed  CAS  Google Scholar 

  88. Entingh-Pearsall A, Kahn CR (2004) Differential roles of the insulin and insulin-like growth factor-I (IGF-I) receptors in response to insulin and IGF-I. J Biol Chem 279:38016–38024

    PubMed  CAS  Google Scholar 

  89. Ergonul Z, Frindt G, Palmer LG (2006) Regulation of maturation and processing of ENaC subunits in the rat kidney. Am J Physiol Renal Physiol 291:F683–F693

    PubMed  CAS  Google Scholar 

  90. Eskandari S, Snyder PM, Kreman M, Zampighi GA, Welsh MJ, Wright EM (1999) Number of subunits comprising the epithelial sodium channel. J Biol Chem 274:27281–27286

    PubMed  CAS  Google Scholar 

  91. Fakitsas P, Adam G, Daidie D, van Bemmelen MX, Fouladkou F, Patrignani A, Wagner U, Warth R, Camargo SM, Staub O, Verrey F (2007) Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation. J Am Soc Nephrol 18:1084–1092

    PubMed  CAS  Google Scholar 

  92. Farman N, Vandewalle A, Bonvalet JP (1982) Aldosterone binding in isolated tubules II. An autoradiographic study of concentration dependency in the rabbit nephron. Am J Physiol 242:F69–F77

    PubMed  CAS  Google Scholar 

  93. Fava C, von Wowern F, Berglund G, Carlson J, Hedblad B, Rosberg L, Burri P, Almgren P, Melander O (2006) 24-h ambulatory blood pressure is linked to chromosome 18q21–22 and genetic variation of NEDD4L associates with cross-sectional and longitudinal blood pressure in Swedes. Kidney Int 70:562–569

    PubMed  CAS  Google Scholar 

  94. Fejes-Toth G, Naray-Fejes-Toth A (2001) Immunohistochemical localization of colonic H-K-ATPase to the apical membrane of connecting tubule cells. Am J Physiol Renal Physiol 281:F318–F325

    PubMed  CAS  Google Scholar 

  95. Fejes-Toth G, Frindt G, Naray-Fejes-Toth A, Palmer LG (2008) Epithelial Na+ channel activation and processing in mice lacking SGK1. Am J Physiol Renal Physiol 294:F1298–F1305

    PubMed  CAS  Google Scholar 

  96. Fenton RA, Brond L, Nielsen S, Praetorius J (2007) Cellular and subcellular distribution of the type-2 vasopressin receptor in the kidney. Am J Physiol Renal Physiol 293:F748–F760

    PubMed  CAS  Google Scholar 

  97. Feraille E, Mordasini D, Gonin S, Deschenes G, Vinciguerra M, Doucet A, Vandewalle A, Summa V, Verrey F, Martin PY (2003) Mechanism of control of Na, K-ATPase in principal cells of the mammalian collecting duct. Ann N Y Acad Sci 986:570–578

    PubMed  CAS  Google Scholar 

  98. Figueroa CD, MacIver AG, Mackenzie JC, Bhoola KD (1988) Localisation of immunoreactive kininogen and tissue kallikrein in the human nephron. Histochemistry 89:437–442

    PubMed  CAS  Google Scholar 

  99. Firsov D, Schild L, Gautschi I, Merillat AM, Schneeberger E, Rossier BC (1996) Cell surface expression of the epithelial Na+ channel and a mutant causing Liddle syndrome: a quantitative approach. Proc Natl Acad Sc U S A 93:15370–15375

    CAS  Google Scholar 

  100. Firsov D, Gautschi I, Merillat AM, Rossier BC, Schild L (1998) The heterotetrameric architecture of the epithelial sodium channel (ENaC). EMBO J 17:344–352

    PubMed  CAS  Google Scholar 

  101. Flores SY, Loffing-Cueni D, Kamynina E, Daidie D, Gerbex C, Chabanel S, Dudler J, Loffing J, Staub O (2005) Aldosterone-induced serum and glucocorticoid-induced kinase 1 expression is accompanied by Nedd4–2 phosphorylation and increased Na+ transport in cortical collecting duct cells. J Am Soc Nephrol 16:2279–2287

    PubMed  CAS  Google Scholar 

  102. Fouladkou F, Alikhani-Koopaei R, Vogt B, Flores SY, Malbert-Colas L, Lecomte MC, Loffing J, Frey FJ, Frey BM, Staub O (2004) A naturally occurring human Nedd4–2 variant displays impaired ENaC regulation in Xenopus laevis oocytes. Am J Physiol Renal Physiol 287:F550–F561

    PubMed  CAS  Google Scholar 

  103. Friedrich B, Feng Y, Cohen P, Risler T, Vandewalle A, Broer S, Wang J, Pearce D, Lang F (2003) The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha, beta, gamma-ENaC. Pflugers Arch 445:693–696

    PubMed  CAS  Google Scholar 

  104. Frindt G, Masilamani S, Knepper MA, Palmer LG (2001) Activation of epithelial Na channels during short-term Na deprivation. Am J Physiol Renal Physiol 280:F112–F118

    PubMed  CAS  Google Scholar 

  105. Frindt G, McNair T, Dahlmann A, Jacobs-Palmer E, Palmer LG (2002) Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol 283:F717–F726

    PubMed  Google Scholar 

  106. Frindt G, Palmer LG (2004) Na channels in the rat connecting tubule. Am J Physiol Renal Physiol 286:F669–F674

    PubMed  CAS  Google Scholar 

  107. Frindt G, Ergonul Z, Palmer LG (2008) Surface expression of epithelial Na channel protein in rat kidney. J Gen Physiol 131:617–627

    PubMed  CAS  Google Scholar 

  108. Fronius M, Clauss WG (2008) Mechano-sensitivity of ENaC: may the (shear) force be with you. Pflugers Arch 455:775–785

    PubMed  CAS  Google Scholar 

  109. Fuller PJ, Young MJ (2005) Mechanisms of mineralocorticoid action. Hypertension 46:1227–1235

    PubMed  CAS  Google Scholar 

  110. Funder JW (2005) Mineralocorticoid receptors: distribution and activation. Heart Fail Rev 10:15–22

    PubMed  CAS  Google Scholar 

  111. Gamba G (2005) Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev 85:423–493

    PubMed  CAS  Google Scholar 

  112. Garg LC, Knepper MA, Burg MB (1981) Mineralocorticoid effects on Na-K-ATPase in individual nephron segments. Am J Physiol 240:F536–F544

    PubMed  CAS  Google Scholar 

  113. Garty H, Edelman IS (1983) Amiloride-sensitive trypsinization of apical sodium channels. Analysis of hormonal regulation of sodium transport in toad bladder. J Gen Physiol 81:785–803

    PubMed  CAS  Google Scholar 

  114. Garty H, Palmer LG (1997) Epithelial sodium channels: function, structure, and regulation. Physiol Rev 77:359–396

    PubMed  CAS  Google Scholar 

  115. Goldfarb SB, Kashlan OB, Watkins JN, Suaud L, Yan W, Kleyman TR, Rubenstein RC (2006) Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels. Proc Natl Acad Sci U S A 103:5817–5822

    PubMed  CAS  Google Scholar 

  116. Gonzalez-Rodriguez E, Gaeggeler HP, Rossier BC (2007) IGF-1 vs insulin: respective roles in modulating sodium transport via the PI-3 kinase/Sgk1 pathway in a cortical collecting duct cell line. Kidney Int 71:116–125

    PubMed  CAS  Google Scholar 

  117. Gormley K, Dong Y, Sagnella GA (2003) Regulation of the epithelial sodium channel by accessory proteins. Biochem J 371:1–14

    PubMed  CAS  Google Scholar 

  118. Goulet CC, Volk KA, Adams CM, Prince LS, Stokes JB, Snyder PM (1998) Inhibition of the epithelial Na+ channel by interaction of Nedd4 with a PY motif deleted in Liddle’s syndrome. J Biol Chem 273:30012–30017

    PubMed  CAS  Google Scholar 

  119. Grahammer F, Artunc F, Sandulache D, Rexhepaj R, Friedrich B, Risler T, McCormick JA, Dawson K, Wang J, Pearce D, Wulff P, Kuhl D, Lang F (2006) Renal function of gene-targeted mice lacking both SGK1 and SGK3. Am J Physiol Regul Integr Comp Physiol 290:R945–R950

    PubMed  CAS  Google Scholar 

  120. Grimm PR, Foutz RM, Brenner R, Sansom SC (2007) Identification and localization of BK-beta subunits in the distal nephron of the mouse kidney. Am J Physiol Renal Physiol 293:F350–F359

    PubMed  CAS  Google Scholar 

  121. Grimm PR, Sansom SC (2007) BK channels in the kidney. Curr Opin Nephrol Hypertens 16:430–436

    PubMed  CAS  Google Scholar 

  122. Guder WG, Hallbach J, Fink E, Kaissling B, Wirthensohn G (1987) Kallikrein (kininogenase) in the mouse nephron: effect of dietary potassium. Biol Chem Hoppe Seyler 368:637–645

    PubMed  CAS  Google Scholar 

  123. Hager H, Kwon TH, Vinnikova AK, Masilamani S, Brooks HL, Frokiaer J, Knepper MA, Nielsen S (2001) Immunocytochemical and immunoelectron microscopic localization of α-, β-, and γ-ENaC in rat kidney. Am J Physiol Renal Physiol 280:F1093–F1106

    PubMed  CAS  Google Scholar 

  124. Hammerman MR, Miller SB (1993) The growth hormone insulin-like growth factor axis in kidney revisited. Am J Physiol 265:F1–F14

    PubMed  CAS  Google Scholar 

  125. Hansen TK, Moller J, Thomsen K, Frandsen E, Dall R, Jorgensen JO, Christiansen JS (2001) Effects of growth hormone on renal tubular handling of sodium in healthy humans. Am J Physiol Endocrinol Metab 281:E1326–E1332

    PubMed  CAS  Google Scholar 

  126. Hanwell D, Ishikawa T, Saleki R, Rotin D (2002) Trafficking and cell surface stability of the epithelial Na+ channel expressed in epithelial Madin–Darby canine kidney cells. J Biol Chem 277:9772–9779

    PubMed  CAS  Google Scholar 

  127. Harris M, Firsov D, Vuagniaux G, Stutts MJ, Rossier BC (2007) A novel neutrophil elastase inhibitor prevents elastase activation and surface cleavage of the epithelial sodium channel expressed in Xenopus laevis oocytes. J Biol Chem 282:58–64

    PubMed  CAS  Google Scholar 

  128. Harris M, Garcia-Caballero A, Stutts MJ, Firsov D, Rossier BC (2008) Preferential assembly of epithelial sodium channel (ENaC) subunits in Xenopus oocytes: role of furin-mediated endogenous proteolysis. J Biol Chem 283:7455–7463

    PubMed  CAS  Google Scholar 

  129. Harrison-Bernard LM, Navar LG, Ho MM, Vinson GP, el-Dahr SS (1997) Immunohistochemical localization of ANG II AT1 receptor in adult rat kidney using a monoclonal antibody. Am J Physiol 273:F170–F177

    PubMed  CAS  Google Scholar 

  130. Hebert SC, Desir G, Giebisch G, Wang W (2005) Molecular diversity and regulation of renal potassium channels. Physiol Rev 85:319–371

    PubMed  CAS  Google Scholar 

  131. Hill WG, An B, Johnson JP (2002) Endogenously expressed epithelial sodium channel is present in lipid rafts in A6 cells. J Biol Chem 277:33541–33544

    PubMed  CAS  Google Scholar 

  132. Hill WG, Butterworth MB, Wang H, Edinger RS, Lebowitz J, Peters KW, Frizzell RA, Johnson JP (2007) The epithelial sodium channel (ENaC) traffics to apical membrane in lipid rafts in mouse cortical collecting duct cells. J Biol Chem 282:37402–37411

    PubMed  CAS  Google Scholar 

  133. Ho KY, Kelly JJ (1991) Role of growth hormone in fluid homeostasis. Horm Res 36(Suppl 1):44–48

    PubMed  Google Scholar 

  134. Hoenderop JG, Nilius B, Bindels RJ (2005) Calcium absorption across epithelia. Physiol Rev 85:373–422

    PubMed  CAS  Google Scholar 

  135. Horisberger JD, Chraibi A (2004) Epithelial sodium channel: a ligand-gated channel? Nephron Physiol 96:37–41

    Google Scholar 

  136. Hou J, Speirs HJ, Seckl JR, Brown RW (2002) Sgk1 gene expression in kidney and its regulation by aldosterone: spatio-temporal heterogeneity and quantitative analysis. J Am Soc Nephrol 13:1190–1198

    PubMed  CAS  Google Scholar 

  137. Howie AJ, Smithson N, Rollason TP (1993) Reconsideration of the development of the distal tubule of the human kidney. J Anat 183(Pt 1):141–147

    PubMed  Google Scholar 

  138. Huang DY, Boini KM, Friedrich B, Metzger M, Just L, Osswald H, Wulff P, Kuhl D, Vallon V, Lang F (2006) Blunted hypertensive effect of combined fructose and high-salt diet in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase SGK1. Am J Physiol Regul Integr Comp Physiol 290:R935–R944

    PubMed  CAS  Google Scholar 

  139. Huang DY, Boini KM, Osswald H, Friedrich B, Artunc F, Ullrich S, Rajamanickam J, Palmada M, Wulff P, Kuhl D, Vallon V, Lang F (2006) Resistance of mice lacking the serum- and glucocorticoid-inducible kinase SGK1 against salt-sensitive hypertension induced by a high-fat diet. Am J Physiol Renal Physiol 291:F1264–F1273

    PubMed  CAS  Google Scholar 

  140. Hughey RP, Bruns JB, Kinlough CL, Harkleroad KL, Tong Q, Carattino MD, Johnson JP, Stockand JD, Kleyman TR (2004) Epithelial sodium channels are activated by furin-dependent proteolysis. J Biol Chem 279:18111–18114

    PubMed  CAS  Google Scholar 

  141. Hughey RP, Bruns JB, Kinlough CL, Kleyman TR (2004) Distinct pools of epithelial sodium channels are expressed at the plasma membrane. J Biol Chem 279:48491–48494

    PubMed  CAS  Google Scholar 

  142. Hughey RP, Carattino MD, Kleyman TR (2007) Role of proteolysis in the activation of epithelial sodium channels. Curr Opin Nephrol Hypertens 16:444–450

    PubMed  CAS  Google Scholar 

  143. Hummler E, Vallon V (2005) Lessons from mouse mutants of epithelial sodium channel and its regulatory proteins. J Am Soc Nephrol 16:3160–3166

    PubMed  CAS  Google Scholar 

  144. Ichimura T, Yamamura H, Sasamoto K, Tominaga Y, Taoka M, Kakiuchi K, Shinkawa T, Takahashi N, Shimada S, Isobe T (2005) 14–3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4–2 ubiquitin ligase. J Biol Chem 280:13187–13194

    PubMed  CAS  Google Scholar 

  145. Imai M (1979) The connecting tubule: a functional subdivision of the rabbit distal nephron segments. Kidney Int 15:346–356

    PubMed  CAS  Google Scholar 

  146. Jasti J, Furukawa H, Gonzales EB, Gouaux E (2007) Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature 449:316–323

    PubMed  CAS  Google Scholar 

  147. Ji HL, Chalfant ML, Jovov B, Lockhart JP, Parker SB, Fuller CM, Stanton BA, Benos DJ (2000) The cytosolic termini of the beta- and gamma-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel. J Biol Chem 275:27947–27956

    PubMed  CAS  Google Scholar 

  148. Ji HL, Benos DJ (2004) Degenerin sites mediate proton activation of δβγ-epithelial sodium channel. J Biol Chem 279:26939–26947

    PubMed  CAS  Google Scholar 

  149. Ji HL, Bishop LR, Anderson SJ, Fuller CM, Benos DJ (2004) The role of Pre-H2 domains of α- and δ-epithelial Na+ channels in ion permeation, conductance, and amiloride sensitivity. J Biol Chem 279:8428–8440

    PubMed  CAS  Google Scholar 

  150. Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ (2006) δ-subunit confers novel biophysical features to α β γ-human ENaC via a physical interaction. J Biol Chem 281:8233–8241

    PubMed  CAS  Google Scholar 

  151. Jiang Q, Li J, Dubroff R, Ahn YJ, Foskett JK, Engelhardt J, Kleyman TR (2000) Epithelial sodium channels regulate cystic fibrosis transmembrane conductance regulator chloride channels in Xenopus oocytes. J Biol Chem 275:13266–13274

    PubMed  CAS  Google Scholar 

  152. Kahle KT, Ring AM, Lifton RP (2008) Molecular physiology of the WNK kinases. Annu Rev Physiol 70:329–355

    PubMed  CAS  Google Scholar 

  153. Kaissling B (1977) Ultrastructural characterization of the connecting tubule and the different segments of the collecting duct system in the rabbit kidney. Curr Probl Clin Biochem 8:435–446

    PubMed  CAS  Google Scholar 

  154. Kaissling B, Kriz W (1979) Structural analysis of the rabbit kidney. Adv Anat Embryol Cell Biol 56:1–123

    PubMed  CAS  Google Scholar 

  155. Kaissling B, Kriz W (1982) Axial heterogeneity of the ‘distal tubule’. Contrib Nephrol 33:29–47

    PubMed  CAS  Google Scholar 

  156. Kaissling B, Le Hir M (1982) Distal tubular segments of the rabbit kidney after adaptation to altered Na- and K-intake. I. Structural changes. Cell Tissue Res 224:469–492

    PubMed  CAS  Google Scholar 

  157. Kaissling B, Kriz W (1992) Morphology of the loop of Henle, distal tubule and collecting duct. In: EE W (ed) Handbook of physiology: section on renal physiology. Oxford University Press, New York, pp 109–167

    Google Scholar 

  158. Kamenicky P, Viengchareun S, Blanchard A, Meduri G, Zizzari P, Imbert-Teboul M, Doucet A, Chanson P, Lombes M (2008) Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegaly. Endocrinology 149:3294–3305

    PubMed  CAS  Google Scholar 

  159. Karpushev AV, Levchenko V, Pavlov TS, Lam VY, Vinnakota KC, Vandewalle A, Wakatsuki T, Staruschenko A (2008) Regulation of ENaC expression at the cell surface by Rab11. Biochem Biophys Res Commun 377:521–525

    PubMed  CAS  Google Scholar 

  160. Katz AI, Doucet A, Morel F (1979) Na-K-ATPase activity along the rabbit, rat, and mouse nephron. Am J Physiol 237:F114–F120

    PubMed  CAS  Google Scholar 

  161. Kellenberger S, Gautschi I, Rossier BC, Schild L (1998) Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system. J Clin Invest 101:2741–2750

    PubMed  CAS  Google Scholar 

  162. Kellenberger S, Schild L (2002) Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev 82:735–767

    PubMed  CAS  Google Scholar 

  163. Kibble JD, Neal AM, Colledge WH, Green R, Taylor CJ (2000) Evidence for cystic fibrosis transmembrane conductance regulator-dependent sodium reabsorption in kidney, using Cftr(tm2cam) mice. J Physiol 526(Pt 1):27–34

    PubMed  CAS  Google Scholar 

  164. Kim J, Kim YH, Cha JH, Tisher CC, Madsen KM (1999) Intercalated cell subtypes in connecting tubule and cortical collecting duct of rat and mouse. J Am Soc Nephrol 10:1–12

    PubMed  CAS  Google Scholar 

  165. Kim SW, Wang W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frokiaer J, Nielsen S (2004) Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats. Am J Physiol Renal Physiol 286:F922–F935

    PubMed  CAS  Google Scholar 

  166. Kim SW, Frokiaer J, Nielsen S (2007) Pathogenesis of oedema in nephrotic syndrome: role of epithelial sodium channel. Nephrology (Carlton) 12(Suppl 3):S8–S10

    CAS  Google Scholar 

  167. Kim YH, Pech V, Spencer KB, Beierwaltes WH, Everett LA, Green ED, Shin W, Verlander JW, Sutliff RL, Wall SM (2007) Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice. Am J Physiol Renal Physiol 293:F1314–F1324

    PubMed  CAS  Google Scholar 

  168. Kleyman TR, Ernst SA, Coupaye-Gerard B (1994) Arginine vasopressin and forskolin regulate apical cell surface expression of epithelial Na+ channels in A6 cells. Am J Physiol 266:F506–F511

    PubMed  CAS  Google Scholar 

  169. Kleyman TR, Myerburg MM, Hughey RP (2006) Regulation of ENaCs by proteases: an increasingly complex story. Kidney Int 70:1391–1392

    PubMed  CAS  Google Scholar 

  170. Knepper MA, Kim GH, Masilamani S (2003) Renal tubule sodium transporter abundance profiling in rat kidney: response to aldosterone and variations in NaCl intake. Ann N Y Acad Sci 986:562–569

    Article  PubMed  CAS  Google Scholar 

  171. Knight KK, Olson DR, Zhou R, Snyder PM (2006) Liddle's syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavage. Proc Natl Acad Sci U S A 103:2805–2808

    PubMed  CAS  Google Scholar 

  172. Kobayashi T, Deak M, Morrice N, Cohen P (1999) Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J 344(Pt 1):189–197

    PubMed  CAS  Google Scholar 

  173. Konig J, Schreiber R, Voelcker T, Mall M, Kunzelmann K (2001) The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits ENaC through an increase in the intracellular Cl− concentration. EMBO Rep 2:1047–1051

    PubMed  CAS  Google Scholar 

  174. Konstas AA, Koch JP, Tucker SJ, Korbmacher C (2002) Cystic fibrosis transmembrane conductance regulator-dependent up-regulation of Kir1.1 (ROMK) renal K+ channels by the epithelial sodium channel. J Biol Chem 277:25377–25384

    PubMed  Google Scholar 

  175. Konstas AA, Shearwin-Whyatt LM, Fotia AB, Degger B, Riccardi D, Cook DI, Korbmacher C, Kumar S (2002) Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4–2-interacting protein. J Biol Chem 277:29406–29416

    PubMed  CAS  Google Scholar 

  176. Konstas AA, Koch JP, Korbmacher C (2003) cAMP-dependent activation of CFTR inhibits the epithelial sodium channel (ENaC) without affecting its surface expression. Pflugers Arch 445(4):513–521

    PubMed  CAS  Google Scholar 

  177. Kosari F, Sheng S, Li J, Mak DO, Foskett JK, Kleyman TR (1998) Subunit stoichiometry of the epithelial sodium channel. J Biol Chem 273:13469–13474

    PubMed  CAS  Google Scholar 

  178. Kumar JM, Brooks DP, Olson BA, Laping NJ (1999) Sgk, a putative serine/threonine kinase, is differentially expressed in the kidney of diabetic mice and humans. J Am Soc Nephrol 10:2488–2494

    PubMed  CAS  Google Scholar 

  179. Kunzelmann K, Schreiber R, Nitschke R, Mall M (2000) Control of epithelial Na+ conductance by the cystic fibrosis transmembrane conductance regulator. Pflugers Arch 440:193–201

    PubMed  CAS  Google Scholar 

  180. Kunzelmann K, Bachhuber T, Regeer R, Markovich D, Sun J, Schreiber R (2005) Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2. FASEB J 19:142–143

    PubMed  CAS  Google Scholar 

  181. Lang F, Klingel K, Wagner CA, Stegen C, Warntges S, Friedrich B, Lanzendorfer M, Melzig J, Moschen I, Steuer S, Waldegger S, Sauter M, Paulmichl M, Gerke V, Risler T, Gamba G, Capasso G, Kandolf R, Hebert SC, Massry SG, Broer S (2000) Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy. Proc Natl Acad Sci U S A 97:8157–8162

    PubMed  CAS  Google Scholar 

  182. Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V (2006) (Patho) physiological significance of the serum- and slucocorticoid-inducible kinase isoforms. Physiol Rev 86:1151–1178

    PubMed  CAS  Google Scholar 

  183. Lau SO, Tkachuck JY, Hasegawa DK, Edson JR (1980) Plasminogen and antithrombin III deficiencies in the childhood nephrotic syndrome associated with plasminogenuria and antithrombinuria. J Pediatr 96:390–392

    PubMed  CAS  Google Scholar 

  184. Le Hir M, Kaissling B, Dubach UC (1982) Distal tubular segments of the rabbit kidney after adaptation to altered Na- and K-intake. II. Changes in Na-K-ATPase activity. Cell Tissue Res 224:493–504

    PubMed  Google Scholar 

  185. Lebowitz J, Edinger RS, An B, Perry CJ, Onate S, Kleyman TR, Johnson JP (2004) IκBkinase-β (IKKBβ) modulation of epithelial sodium channel activity. J Biol Chem 279:41985–41990

    PubMed  CAS  Google Scholar 

  186. Lee IH, Dinudom A, Sanchez-Perez A, Kumar S, Cook DI (2007) Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4–2. J Biol Chem 282:29866–29873

    PubMed  CAS  Google Scholar 

  187. Lee IH, Campbell CR, Cook DI, Dinudom A (2008) Regulation of epithelial Na+ channels by aldosterone: role of Sgk1. Clin Exp Pharmacol Physiol 35:235–241

    PubMed  CAS  Google Scholar 

  188. Lehrmann H, Thomas J, Kim SJ, Jacobi C, Leipziger J (2002) Luminal P2Y2 receptor-mediated inhibition of Na+ absorption in isolated perfused mouse CCD. J Am Soc Nephrol 13:10–18

    PubMed  CAS  Google Scholar 

  189. Letz B, Korbmacher C (1997) cAMP stimulates CFTR-like Cl− channels and inhibits amiloride-sensitive Na+ channels in mouse CCD cells. Am J Physiol 272:C657–C666

    PubMed  CAS  Google Scholar 

  190. Lewis SA, Alles WP (1986) Urinary kallikrein: a physiological regulator of epithelial Na+ absorption. Proc Natl Acad Sci U S A 83:5345–5348

    PubMed  CAS  Google Scholar 

  191. Li Y, Konings IB, Zhao J, Price LS, de Heer E, Deen PM (2008) Renal expression of exchange protein directly activated by cAMP (Epac) 1 and 2. Am J Physiol Renal Physiol 295:F525–F533

    PubMed  CAS  Google Scholar 

  192. Liang X, Peters KW, Butterworth MB, Frizzell RA (2006) 14-3-3 isoforms are induced by aldosterone and participate in its regulation of epithelial sodium channels. J Biol Chem 281:16323–16332

    PubMed  CAS  Google Scholar 

  193. Liddle GW, Bledsoe T, Coppage WS (1963) A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Physicians 76:199–213

    CAS  Google Scholar 

  194. Lifton RP, Gharavi AG, Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104:545–556

    PubMed  CAS  Google Scholar 

  195. Loffing-Cueni D, Flores SY, Sauter D, Daidie D, Siegrist N, Meneton P, Staub O, Loffing J (2006) Dietary sodium intake regulates the ubiquitin-protein ligase Nedd4–2 in the renal collecting system. J Am Soc Nephrol 17:1264–1274

    PubMed  CAS  Google Scholar 

  196. Loffing J, Loffing-Cueni D, Macher A, Hebert SC, Olson B, Knepper MA, Rossier BC, Kaissling B (2000) Localization of epithelial sodium channel and aquaporin-2 in rabbit kidney cortex. Am J Physiol Renal Physiol 278:F530–F539

    PubMed  CAS  Google Scholar 

  197. Loffing J, Pietri L, Aregger F, Bloch-Faure M, Ziegler U, Meneton P, Rossier BC, Kaissling B (2000) Differential subcellular localization of ENaC subunits in mouse kidney in response to high- and low-Na diets. Am J Physiol Renal Physiol 279:F252–F258

    PubMed  CAS  Google Scholar 

  198. Loffing J, Zecevic M, Feraille E, Kaissling B, Asher C, Rossier BC, Firestone GL, Pearce D, Verrey F (2001) Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK. Am J Physiol Renal Physiol 280:F675–F682

    PubMed  CAS  Google Scholar 

  199. Loffing J, Kaissling B (2003) Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human. Am J Physiol Renal Physiol 284:F628–F643

    PubMed  CAS  Google Scholar 

  200. Loffing J, Vallon V, Loffing-Cueni D, Aregger F, Richter K, Pietri L, Bloch-Faure M, Hoenderop JG, Shull GE, Meneton P, Kaissling B (2004) Altered renal distal tubule structure and renal Na+ and Ca2+ handling in a mouse model for Gitelman's syndrome. J Am Soc Nephrol 15:2276–2288

    PubMed  CAS  Google Scholar 

  201. Loffing J, Flores SY, Staub O (2006) Sgk kinases and their role in epithelial transport. Annu Rev Physiol 68:461–490

    PubMed  CAS  Google Scholar 

  202. Lourdel S, Loffing J, Favre G, Paulais M, Nissant A, Fakitsas P, Creminon C, Feraille E, Verrey F, Teulon J, Doucet A, Deschenes G (2005) Hyperaldosteronemia and activation of the apithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis. J Am Soc Nephrol 16:3642–3650

    PubMed  CAS  Google Scholar 

  203. Lu C, Jiang C, Pribanic S, Rotin D (2007) CFTR stabilizes ENaC at the plasma membrane. J Cyst Fibros 6:419–422

    PubMed  Google Scholar 

  204. Lu C, Pribanic S, Debonneville A, Jiang C, Rotin D (2007) The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. Traffic 8:1246–1264

    PubMed  CAS  Google Scholar 

  205. Madala Halagappa VK, Tiwari S, Riazi S, Hu X, Ecelbarger CM (2008) Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat. Am J Physiol Renal Physiol 294:F1222–F1231

    PubMed  Google Scholar 

  206. Madsen KM, Tisher CC (1986) Structural–functional relationship along the distal nephron. Am J Physiol 250:F1–F15

    CAS  Google Scholar 

  207. Madsen KM, Verlander JW, Tisher CC (1988) Relationship between structure and function in distal tubule and collecting duct. J Electron Microsc Tech 9:187–208

    PubMed  CAS  Google Scholar 

  208. Malik B, Price SR, Mitch WE, Yue Q, Eaton DC (2006) Regulation of epithelial sodium channels by the ubiquitin-proteasome proteolytic pathway. Am J Physiol Renal Physiol 290:F1285–F1294

    PubMed  CAS  Google Scholar 

  209. Mall M, Grubb BR, Harkema JR, O'Neal WK, Boucher RC (2004) Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 10:487–493

    PubMed  CAS  Google Scholar 

  210. Malnic G, Klose RM, Giebisch G (1966) Micropuncture study of distal tubular potassium and sodium transport in rat nephron. Am J Physiol 211:529–547

    PubMed  CAS  Google Scholar 

  211. Marchetti J, Imbert-Teboul M, Alhenc-Gelas F, Allegrini J, Menard J, Morel F (1984) Kallikrein along the rabbit microdissected nephron: a micromethod for its measurement. Effect of adrenalectomy and DOCA treatment. Pflugers Arch 401:27–33

    PubMed  CAS  Google Scholar 

  212. Margolius H, Geller R, Pisano J, Sjoerdsma A (1971) Altered urinary kallikrein excretion in human hypertension. The Lancet 2:1063–1065

    Google Scholar 

  213. Marunaka Y, Hagiwara N, Tohda H (1992) Insulin activates single amiloride-blockable Na channels in a distal nephron cell line (A6). Am J Physiol 263:F392–F400

    PubMed  CAS  Google Scholar 

  214. Masilamani S, Kim GH, Mitchell C, Wade JB, Knepper MA (1999) Aldosterone-mediated regulation of ENaC α, β, and γ subunit proteins in rat kidney. J Clin Invest 104:R19–R23

    PubMed  CAS  Google Scholar 

  215. Mastroberardino L, Spindler B, Forster I, Loffing J, Assandri R, May A, Verrey F (1998) Ras pathway activates epithelial Na+ channel and decreases its surface expression in Xenopus oocytes. Mol Biol Cell 9:3417–3427

    PubMed  CAS  Google Scholar 

  216. Matsumoto PS, Ohara A, Duchatelle P, Eaton DC (1993) Tyrosine kinase regulates epithelial sodium transport in A6 cells. Am J Physiol 264:C246–C250

    PubMed  CAS  Google Scholar 

  217. May A, Puoti A, Gaeggeler HP, Horisberger JD, Rossier BC (1997) Early effect of aldosterone on the rate of synthesis of the epithelial sodium channel alpha subunit in A6 renal cells. J Am Soc Nephrol 8:1813–1822

    PubMed  CAS  Google Scholar 

  218. McCormick JA, Feng Y, Dawson K, Behne MJ, Yu B, Wang J, Wyatt AW, Henke G, Grahammer F, Mauro TM, Lang F, Pearce D (2004) Targeted disruption of the protein kinase SGK3/CISK impairs postnatal hair follicle development. Mol Biol Cell 15:4278–4288

    PubMed  CAS  Google Scholar 

  219. McEneaney V, Harvey BJ, Thomas W (2008) Aldosterone regulates rapid trafficking of epithelial sodium channel subunits in renal cortical collecting duct cells via protein kinase D activation. Mol Endocrinol 22:881–892

    PubMed  CAS  Google Scholar 

  220. Meneton P, Loffing J, Warnock DG (2004) Sodium and potassium handling by the aldosterone-sensitive distal nephron: the pivotal role of the distal and connecting tubule. Am J Physiol Renal Physiol 287:F593–F601

    PubMed  CAS  Google Scholar 

  221. Mennitt PA, Wade JB, Ecelbarger CA, Palmer LG, Frindt G (1997) Localization of ROMK channels in the rat kidney. J Am Soc Nephrol 8:1823–1830

    PubMed  CAS  Google Scholar 

  222. Moller J, Jorgensen JO, Marqversen J, Frandsen E, Christiansen JS (2000) Insulin-like growth factor I administration induces fluid and sodium retention in healthy adults: possible involvement of renin and atrial natriuretic factor. Clin Endocrinol (Oxf) 52:181–186

    CAS  Google Scholar 

  223. Morel F (1981) Sites of hormone action in the mammalian nephron. Am J Physiol 240:F159–F164

    PubMed  CAS  Google Scholar 

  224. Morimoto T, Liu W, Woda C, Carattino MD, Wei Y, Hughey RP, Apodaca G, Satlin LM, Kleyman TR (2006) Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct. Am J Physiol Renal Physiol 291:F663–F669

    PubMed  CAS  Google Scholar 

  225. Morris RG, Schafer JA (2002) cAMP increases density of ENaC subunits in the apical membrane of MDCK cells in direct proportion to amiloride-sensitive Na+ transport. J Gen Physiol 120:71–85

    PubMed  CAS  Google Scholar 

  226. Morsing P, Velazquez H, Ellison D, Wright FS (1993) Resetting of tubuloglomerular feedback by interrupting early distal flow. Acta Physiol Scand 148:63–68

    PubMed  CAS  Google Scholar 

  227. Mujais SK, Kauffman S, Katz AI (1986) Angiotensin II binding sites in individual segments of the rat nephron. J Clin Invest 77:315–318

    PubMed  CAS  Google Scholar 

  228. Mutig K, Paliege A, Kahl T, Jons T, Muller-Esterl W, Bachmann S (2007) Vasopressin V2 receptor expression along rat, mouse, and human renal epithelia with focus on TAL. Am J Physiol Renal Physiol 293:F1166–F1177

    PubMed  CAS  Google Scholar 

  229. Nagaki K, Yamamura H, Shimada S, Saito T, Hisanaga S, Taoka M, Isobe T, Ichimura T (2006) 14-3-3 Mediates phosphorylation-dependent inhibition of the interaction between the ubiquitin E3 ligase Nedd4–2 and epithelial Na+ channels. Biochemistry 45:6733–6740

    PubMed  CAS  Google Scholar 

  230. Nagel G, Szellas T, Riordan JR, Friedrich T, Hartung K (2001) Non-specific activation of the epithelial sodium channel by the CFTR chloride channel. EMBO Rep 2:249–254

    PubMed  CAS  Google Scholar 

  231. Nagy Z, Busjahn A, Bahring S, Faulhaber HD, Gohlke HR, Knoblauch H, Rosenthal M, Muller-Myhsok B, Schuster H, Luft FC (1999) Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man. J Am Soc Nephrol 10:1709–1716

    PubMed  CAS  Google Scholar 

  232. Naray-Fejes-Toth A, Canessa C, Cleaveland ES, Aldrich G, Fejes-Toth G (1999) sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial Na+ channels. J Biol Chem 274:16973–16978

    PubMed  CAS  Google Scholar 

  233. Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K, Shiraishi N, Nonoguchi H, Chen LM, Chai KX, Chao J, Tomita K (2002) Regulation of prostasin by aldosterone in the kidney. J Clin Invest 109:401–408

    PubMed  CAS  Google Scholar 

  234. Neiss WF, Klehn KL (1981) The postnatal development of the rat kidney, with special reference to the chemodifferentiation of the proximal tubule. Histochemistry 73:251–268

    PubMed  CAS  Google Scholar 

  235. Nesterov V, Dahlmann A, Bertog M, Korbmacher C (2008) Trypsin can activate the epithelial sodium channel (ENaC) in microdissected mouse distal nephron. Am J Physiol Renal Physiol 295:F1052–F1062

    PubMed  CAS  Google Scholar 

  236. Nicco C, Wittner M, DiStefano A, Jounier S, Bankir L, Bouby N (2001) Chronic exposure to vasopressin upregulates ENaC and sodium transport in the rat renal collecting duct and lung. Hypertension 38:1143–1149

    PubMed  CAS  Google Scholar 

  237. Nicod M, Michlig S, Flahaut M, Salinas M, Fowler Jaeger N, Horisberger JD, Rossier BC, Firsov D (2002) A novel vasopressin-induced transcript promotes MAP kinase activation and ENaC downregulation. EMBO J 21:5109–5117

    PubMed  CAS  Google Scholar 

  238. Nielsen J, Kwon TH, Masilamani S, Beutler K, Hager H, Nielsen S, Knepper MA (2002) Sodium transporter abundance profiling in kidney: effect of spironolactone. Am J Physiol Renal Physiol 283:F923–F933

    PubMed  Google Scholar 

  239. Nielsen J, Kwon TH, Frokiaer J, Knepper MA, Nielsen S (2007) Maintained ENaC trafficking in aldosterone-infused rats during mineralocorticoid and glucocorticoid receptor blockade. Am J Physiol Renal Physiol 292:F382–F394

    PubMed  CAS  Google Scholar 

  240. Oda T, Hotta O, Taguma Y, Kitamura H, Sudo K, Horigome I, Chiba S, Yoshizawa N, Nagura H (1997) Involvement of neutrophil elastase in crescentic glomerulonephritis. Hum Pathol 28:720–728

    PubMed  CAS  Google Scholar 

  241. Olivieri O, Castagna A, Guarini P, Chiecchi L, Sabaini G, Pizzolo F, Corrocher R, Righetti PG (2005) Urinary prostasin: a candidate marker of epithelial sodium channel activation in humans. Hypertension 46:683–688

    PubMed  CAS  Google Scholar 

  242. Omata K, Carretero OA, Itoh S, Scicli AG (1983) Active and inactive kallikrein in rabbit connecting tubules and urine during low and normal sodium intake. Kidney Int 24:714–718

    PubMed  CAS  Google Scholar 

  243. Orce GG, Castillo GA, Margolius HS (1980) Inhibition of short-circuit current in toad urinary bladder by inhibitors of glandular kallikrein. Am J Physiol 239:F459–F465

    PubMed  CAS  Google Scholar 

  244. Osathanondh V, Potter EL (1966) Development of human kidney as shown by microdissection. IV. Development of tubular portions of nephrons. Arch Pathol 82:391–402

    PubMed  CAS  Google Scholar 

  245. Pacha J, Frindt G, Antonian L, Silver RB, Palmer LG (1993) Regulation of Na channels of the rat cortical collecting tubule by aldosterone. J Gen Physiol 102:25–42

    PubMed  CAS  Google Scholar 

  246. Palmer LG, Frindt G (2007) Na+ and K+ transport by the renal connecting tubule. Curr Opin Nephrol Hypertens 16:477–483

    PubMed  CAS  Google Scholar 

  247. Palmer LG, Frindt G (2007) High-conductance K channels in intercalated cells of the rat distal nephron. Am J Physiol Renal Physiol 292:F966–F973

    PubMed  CAS  Google Scholar 

  248. Passero CJ, Mueller GM, Rondon-Berrios H, Tofovic SP, Hughey RP, Kleyman TR (2008) Plasmin activates epithelial Na+ channels by cleaving the γ subunit. J Biol Chem 283:36586–36591

    PubMed  CAS  Google Scholar 

  249. Pearce D (2003) SGK1 regulation of epithelial sodium transport. Cell Physiol Biochem 13:13–20

    PubMed  CAS  Google Scholar 

  250. Perrotti N, He RA, Phillips SA, Haft CR, Taylor SI (2001) Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. J Biol Chem 276:9406–9412

    PubMed  CAS  Google Scholar 

  251. Peti-Peterdi J, Warnock DG, Bell PD (2002) Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors. J Am Soc Nephrol 13:1131–1135

    PubMed  CAS  Google Scholar 

  252. Picard N, Eladari D, El Moghrabi S, Planes C, Bourgeois S, Houillier P, Wang Q, Burnier M, Deschenes G, Knepper MA, Meneton P, Chambrey R (2008) Defective ENaC processing and function in tissue kallikrein-deficient mice. J Biol Chem 283:4602–4611

    PubMed  CAS  Google Scholar 

  253. Piedagnel R, Tiger Y, Lelongt B, Ronco PM (2006) Urokinase (u-PA) is produced by collecting duct principal cells and is post-transcriptionally regulated by SV40 large-T, arginine vasopressin, and epidermal growth factor. J Cell Physiol 206:394–401

    PubMed  CAS  Google Scholar 

  254. Planes C, Caughey GH (2007) Regulation of the epithelial Na+ channel by peptidases. Curr Top Dev Biol 78:23–46

    PubMed  CAS  Google Scholar 

  255. Plant PJ, Lafont F, Lecat S, Verkade P, Simons K, Rotin D (2000) Apical membrane targeting of Nedd4 is mediated by an association of its C2 domain with annexin XIIIb. J Cell Biol 149:1473–1484

    PubMed  CAS  Google Scholar 

  256. Pochynyuk O, Staruschenko A, Tong Q, Medina J, Stockand JD (2005) Identification of a functional phosphatidylinositol 3, 4, 5-trisphosphate binding site in the epithelial Na+ channel. J Biol Chem 280:37565–37571

    PubMed  CAS  Google Scholar 

  257. Pochynyuk O, Tong Q, Staruschenko A, Ma HP, Stockand JD (2006) Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides. Am J Physiol Renal Physiol 290:F949–F957

    PubMed  CAS  Google Scholar 

  258. Pochynyuk O, Tong Q, Medina J, Vandewalle A, Staruschenko A, Bugaj V, Stockand JD (2007) Molecular determinants of PI(4, 5) P2 and PI(3, 4, 5) P3 regulation of the epithelial Na+ channel. J Gen Physiol 130:399–413

    PubMed  CAS  Google Scholar 

  259. Pochynyuk O, Bugaj V, Rieg T, Insel PA, Mironova E, Vallon V, Stockand JD (2008) Paracrine regulation of the epithelial Na+ channel in the mammalian collecting duct by purinergic P2Y2 receptor tone. J Biol Chem 283:36599–36607

    PubMed  CAS  Google Scholar 

  260. Pochynyuk O, Bugaj V, Stockand JD (2008) Physiologic regulation of the epithelial sodium channel by phosphatidylinositides. Curr Opin Nephrol Hypertens 17:533–540

    PubMed  CAS  Google Scholar 

  261. Pochynyuk O, Bugaj V, Vandewalle A, Stockand JD (2008) Purinergic control of apical plasma membrane PI(4, 5) P2 levels sets ENaC activity in principal cells. Am J Physiol Renal Physiol 294:F38–F46

    PubMed  CAS  Google Scholar 

  262. Proud D, Knepper MA, Pisano JJ (1983) Distribution of immunoreactive kallikrein along the rat nephron. Am J Physiol 244:F510–F515

    PubMed  CAS  Google Scholar 

  263. Qi J, Peters KW, Liu C, Wang JM, Edinger RS, Johnson JP, Watkins SC, Frizzell RA (1999) Regulation of the amiloride-sensitive epithelial sodium channel by syntaxin 1A. J Biol Chem 274:30345–30348

    PubMed  CAS  Google Scholar 

  264. Raciti D, Reggiani L, Geffers L, Jiang Q, Bacchion F, Subrizi AE, Clements D, Tindal C, Davidson DR, Kaissling B, Brandli AW (2008) Organization of the pronephric kidney revealed by large-scale gene expression mapping. Genome Biol 9:R84

    PubMed  Google Scholar 

  265. Rauh R, Dinudom A, Fotia AB, Paulides M, Kumar S, Korbmacher C, Cook DI (2006) Stimulation of the epithelial sodium channel (ENaC) by the serum- and glucocorticoid-inducible kinase (Sgk) involves the PY motifs of the channel but is independent of sodium feedback inhibition. Pflugers Arch 452:290–299

    PubMed  CAS  Google Scholar 

  266. Reddy MM, Light MJ, Quinton PM (1999) Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl− channel function. Nature 402:301–304

    PubMed  CAS  Google Scholar 

  267. Reif MC, Troutman SL, Schafer JA (1986) Sodium transport by rat cortical collecting tubule. Effects of vasopressin and desoxycorticosterone. J Clin Invest 77:1291–1298

    PubMed  CAS  Google Scholar 

  268. Reilly RF, Ellison DH (2000) Mammalian distal tubule: physiology, pathophysiology, and molecular anatomy. Physiol Rev 80:277–313

    PubMed  CAS  Google Scholar 

  269. Ren Y, Garvin JL, Liu R, Carretero OA (2007) Crosstalk between the connecting tubule and the afferent arteriole regulates renal microcirculation. Kidney Int 71:1116–1121

    PubMed  CAS  Google Scholar 

  270. Ren Y, D’Ambrosio MA, Garvin JL, Wang H, Carretero OA (2009) Possible mediators of connecting tubule glomerular feedback. Hypertension 53:319

    PubMed  CAS  Google Scholar 

  271. Renard S, Lingueglia E, Voilley N, Lazdunski M, Barbry P (1994) Biochemical analysis of the membrane topology of the amiloride-sensitive Na+ channel. J Biol Chem 269:12981–12986

    PubMed  CAS  Google Scholar 

  272. Riazi S, Khan O, Hu X, Ecelbarger CA (2006) Aldosterone infusion with high-NaCl diet increases blood pressure in obese but not lean Zucker rats. Am J Physiol Renal Physiol 291:F597–F605

    PubMed  CAS  Google Scholar 

  273. Riazi S, Khan O, Tiwari S, Hu X, Ecelbarger CA (2006) Rosiglitazone regulates ENaC and Na-K-2Cl cotransporter (NKCC2) abundance in the obese Zucker rat. Am J Nephrol 26:245–257

    PubMed  CAS  Google Scholar 

  274. Riazi S, Madala-Halagappa VK, Hu X, Ecelbarger CA (2006) Sex and body-type interactions in the regulation of renal sodium transporter levels, urinary excretion, and activity in lean and obese Zucker rats. Gend Med 3:309–327

    PubMed  Google Scholar 

  275. Riazi S, Maric C, Ecelbarger CA (2006) 17-Beta Estradiol attenuates streptozotocin-induced diabetes and regulates the expression of renal sodium transporters. Kidney Int 69:471–480

    PubMed  CAS  Google Scholar 

  276. Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, Vallon V (2007) Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J 21:3717–3726

    PubMed  CAS  Google Scholar 

  277. Robert-Nicoud M, Flahaut M, Elalouf JM, Nicod M, Salinas M, Bens M, Doucet A, Wincker P, Artiguenave F, Horisberger JD, Vandewalle A, Rossier BC, Firsov D (2001) Transcriptome of a mouse kidney cortical collecting duct cell line: effects of aldosterone and vasopressin. Proc Natl Acad Sci U S A 98:2712–2716

    PubMed  CAS  Google Scholar 

  278. Rohrwasser A, Morgan T, Dillon HF, Zhao L, Callaway CW, Hillas E, Zhang S, Cheng T, Inagami T, Ward K, Terreros DA, Lalouel JM (1999) Elements of a paracrine tubular renin-angiotensin system along the entire nephron. Hypertension 34:1265–1274

    PubMed  CAS  Google Scholar 

  279. Ronzaud C, Loffing J, Bleich M, Gretz N, Grone HJ, Schutz G, Berger S (2007) Impairment of sodium balance in mice deficient in renal principal cell mineralocorticoid receptor. J Am Soc Nephrol 18:1679–1687

    PubMed  CAS  Google Scholar 

  280. Rossier BC (2002) Hormonal regulation of the epithelial sodium channel ENaC: N or P(o)? J Gen Physiol 120:67–70

    PubMed  CAS  Google Scholar 

  281. Rossier BC (2004) The epithelial sodium channel: activation by membrane-bound serine proteases. Proc Am Thorac Soc 1:4–9

    PubMed  CAS  Google Scholar 

  282. Rossier BC, Schild L (2008) Epithelial sodium channel: mendelian versus essential hypertension. Hypertension 52:595–600

    PubMed  CAS  Google Scholar 

  283. Rossier BC, Stutts MJ (2009) Activation of the epithelial sodium channel (ENaC) by serine proteases. Annu Rev Physiol 71:16.1–16.19

    Google Scholar 

  284. Rotin D (2000) Regulation of the epithelial sodium channel (ENaC) by accessory proteins. Curr Opin Nephrol Hypertens 9:529–534

    PubMed  CAS  Google Scholar 

  285. Rotin D (2008) Role of the UPS in Liddle syndrome. BMC Biochem 9(Suppl 1):S5

    PubMed  Google Scholar 

  286. Rotin D, Schild L (2008) ENaC and its regulatory proteins as drug targets for blood pressure control. Curr Drug Targets 9:709–716

    PubMed  CAS  Google Scholar 

  287. Rubera I, Loffing J, Palmer LG, Frindt G, Fowler-Jaeger N, Sauter D, Carroll T, McMahon A, Hummler E, Rossier BC (2003) Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance. J Clin Invest 112:554–565

    PubMed  CAS  Google Scholar 

  288. Rubera I, Hummler E, Beermann F (2008) Transgenic mice and their impact on kidney research. Pflugers Arch (in press)

  289. Ruffieux-Daidie D, Poirot O, Boulkroun S, Verrey F, Kellenberger S, Staub O (2008) Deubiquitylation regulates activation and proteolytic cleavage of ENaC. J Am Soc Nephrol 19:2170–2180

    PubMed  CAS  Google Scholar 

  290. Sabirov RZ, Okada Y (2005) ATP release via anion channels. Purinergic Signal 1:311–328

    PubMed  CAS  Google Scholar 

  291. Sagnella GA, Swift PA (2006) The renal epithelial sodium channel: genetic heterogeneity and implications for the treatment of high blood pressure. Curr Pharm Des 12:2221–2234

    PubMed  CAS  Google Scholar 

  292. Sauter D, Fernandes S, Goncalves-Mendes N, Boulkroun S, Bankir L, Loffing J, Bouby N (2006) Long-term effects of vasopressin on the subcellular localization of ENaC in the renal collecting system. Kidney Int 69:1024–1032

    PubMed  CAS  Google Scholar 

  293. Sawicki PT, Heinemann L, Starke A, Berger M (1992) Hyperinsulinaemia is not linked with blood pressure elevation in patients with insulinoma. Diabetologia 35:649–652

    PubMed  CAS  Google Scholar 

  294. Saxena S, Singh M, Engisch K, Fukuda M, Kaur S (2005) Rab proteins regulate epithelial sodium channel activity in colonic epithelial HT-29 cells. Biochem Biophys Res Commun 337:1219–1223

    PubMed  CAS  Google Scholar 

  295. Saxena SK, George CM, Pinskiy V, McConnell B (2006) Epithelial sodium channel is regulated by SNAP-23/syntaxin 1A interplay. Biochem Biophys Res Commun 343:1279–1285

    PubMed  CAS  Google Scholar 

  296. Saxena SK, Horiuchi H, Fukuda M (2006) Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism. Biochem Biophys Res Commun 344:651–657

    PubMed  CAS  Google Scholar 

  297. Saxena SK, Singh M, Shibata H, Kaur S, George C (2006) Rab4 GTP/GDP modulates amiloride-sensitive sodium channel (ENaC) function in colonic epithelia. Biochem Biophys Res Commun 340:726–733

    PubMed  CAS  Google Scholar 

  298. Schafer JA, Hawk CT (1992) Regulation of Na+ channels in the cortical collecting duct by AVP and mineralocorticoids. Kidney Int 41:255–268

    PubMed  CAS  Google Scholar 

  299. Schmitt R, Ellison DH, Farman N, Rossier BC, Reilly RF, Reeves WB, Oberbaumer I, Tapp R, Bachmann S (1999) Developmental expression of sodium entry pathways in rat nephron. Am J Physiol 276:F367–F381

    PubMed  CAS  Google Scholar 

  300. Scicli AG, Rabito SF, Carretero OA (1983) Blood and urinary kinins in human subjects during normal and low sodium intake. Adv Exp Med Biol 156(Pt B):877–882

    PubMed  Google Scholar 

  301. Sheng S, Carattino MD, Bruns JB, Hughey RP, Kleyman TR (2006) Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition. Am J Physiol Renal Physiol 290:F1488–F1496

    PubMed  CAS  Google Scholar 

  302. Sheng S, Johnson JP, Kleyman TR (2007) Epithelial Na+ channels. In: Alpern RJ, Hebert SC (eds) Seldin and Giebisch's the kidney. Elsevier, Amsterdam, pp 889–924

    Google Scholar 

  303. Shi H, Asher C, Chigaev A, Yung Y, Reuveny E, Seger R, Garty H (2002) Interactions of beta and gamma ENaC with Nedd4 can be facilitated by an ERK-mediated phosphorylation. J Biol Chem 277:13539–13547

    PubMed  CAS  Google Scholar 

  304. Shi H, Asher C, Yung Y, Kligman L, Reuveny E, Seger R, Garty H (2002) Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunits. Eur J Biochem 269:4551–4558

    PubMed  CAS  Google Scholar 

  305. Shi PP, Cao XR, Sweezer EM, Kinney TS, Williams NR, Husted RF, Nair R, Weiss RM, Williamson RA, Sigmund CD, Snyder PM, Staub O, Stokes JB, Yang B (2008) Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4–2. Am J Physiol Renal Physiol 295:F462–F470

    PubMed  CAS  Google Scholar 

  306. Shigaev A, Asher C, Latter H, Garty H, Reuveny E (2000) Regulation of sgk by aldosterone and its effects on the epithelial Na+ channel. Am J Physiol Renal Physiol 278:F613–F619

    PubMed  CAS  Google Scholar 

  307. Shimkets RA, Lifton R, Canessa CM (1998) In vivo phosphorylation of the epithelial sodium channel. Proc Natl Acad Sci U S A 95:3301–3305

    PubMed  CAS  Google Scholar 

  308. Silver RB, Frindt G (1993) Functional identification of H-K-ATPase in intercalated cells of cortical collecting tubule. Am J Physiol 264:F259–F266

    PubMed  CAS  Google Scholar 

  309. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    PubMed  CAS  Google Scholar 

  310. Snyder PM, Cheng C, Prince LS, Rogers JC, Welsh MJ (1998) Electrophysiological and biochemical evidence that DEG/ENaC cation channels are composed of nine subunits. J Biol Chem 273:681–684

    PubMed  CAS  Google Scholar 

  311. Snyder PM, Olson DR, Thomas BC (2002) Serum and glucocorticoid-regulated kinase modulates Nedd4–2-mediated inhibition of the epithelial Na+ channel. J Biol Chem 277:5–8

    PubMed  CAS  Google Scholar 

  312. Snyder PM, Olson DR, Kabra R, Zhou R, Steines JC (2004) cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na+ channel through convergent phosphorylation of Nedd4–2. J Biol Chem 279:45753–45758

    PubMed  CAS  Google Scholar 

  313. Snyder PM (2005) Minireview: regulation of epithelial Na+ channel trafficking. Endocrinology 146:5079–5085

    PubMed  CAS  Google Scholar 

  314. Song J, Hu X, Riazi S, Tiwari S, Wade JB, Ecelbarger CA (2006) Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key renal sodium transporters by chronic insulin infusion in rats. Am J Physiol Renal Physiol 290:F1055–F1064

    PubMed  CAS  Google Scholar 

  315. Soundararajan R, Zhang TT, Wang J, Vandewalle A, Pearce D (2005) A novel role for glucocorticoid-induced leucine zipper protein in epithelial sodium channel-mediated sodium transport. J Biol Chem 280:39970–39981

    PubMed  CAS  Google Scholar 

  316. Soundararajan R, Wang J, Melters D, Pearce D (2007) Differential activities of glucocorticoid-induced leucine zipper protein isoforms. J Biol Chem 282:36303–36313

    PubMed  CAS  Google Scholar 

  317. Staruschenko A, Pochynyuk O, Vandewalle A, Bugaj V, Stockand JD (2007) Acute regulation of the epithelial Na+ channel by phosphatidylinositide 3-OH kinase signaling in native collecting duct principal cells. J Am Soc Nephrol 18:1652–1661

    PubMed  CAS  Google Scholar 

  318. Staub O, Rotin D (2006) Role of ubiquitylation in cellular membrane transport. Physiol Rev 86:669–707

    PubMed  CAS  Google Scholar 

  319. Stutts MJ, Canessa CM, Olsen JC, Hamrick M, Cohn JA, Rossier BC, Boucher RC (1995) CFTR as a cAMP-dependent regulator of sodium channels. Science 269:847–850

    PubMed  CAS  Google Scholar 

  320. Svenningsen P, Bistrup C, Friis UG, Bertog M, Haerteis S, Krueger B, Stubbe J, Jensen ON, Thiesson HC, Uhrenholt TR, Jespersen B, Jensen BL, Korbmacher C, Skott O (2009) Plasmin in nephrotic urine activates the epithelial sodium channel. J Am Soc Nephrol 20:299–310

    PubMed  CAS  Google Scholar 

  321. Tashiro K, Koyanagi I, Ohara I, Ito T, Saitoh A, Horikoshi S, Tomino Y (2004) Levels of urinary matrix metalloproteinase-9 (MMP-9) and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal 18:206–210

    PubMed  CAS  Google Scholar 

  322. Thomas CP, Itani OA (2004) New insights into epithelial sodium channel function in the kidney: site of action, regulation by ubiquitin ligases, serum- and glucocorticoid-inducible kinase and proteolysis. Curr Opin Nephrol Hypertens 13:541–548

    PubMed  CAS  Google Scholar 

  323. Thomas G (2002) Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 3:753–766

    PubMed  CAS  Google Scholar 

  324. Tiwari S, Halagappa VK, Riazi S, Hu X, Ecelbarger CA (2007) Reduced expression of insulin receptors in the kidneys of insulin-resistant rats. J Am Soc Nephrol 18:2661–2671

    PubMed  CAS  Google Scholar 

  325. Tiwari S, Nordquist L, Halagappa VK, Ecelbarger CA (2007) Trafficking of ENaC subunits in response to acute insulin in mouse kidney. Am J Physiol Renal Physiol 293:F178–F185

    PubMed  CAS  Google Scholar 

  326. Tiwari S, Sharma N, Gill PS, Igarashi P, Kahn CR, Wade JB, Ecelbarger CM (2008) Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor. Proc Natl Acad Sci U S A 105:6469–6474

    PubMed  CAS  Google Scholar 

  327. Todd-Turla KM, Rusvai E, Naray-Fejes-Toth A, Fejes-Toth G (1996) CFTR expression in cortical collecting duct cells. Am J Physiol 270:F237–F244

    PubMed  CAS  Google Scholar 

  328. Tomita K, Pisano JJ, Knepper MA (1985) Control of sodium and potassium transport in the cortical collecting duct of the rat. Effects of bradykinin, vasopressin, and deoxycorticosterone. J Clin Invest 76:132–136

    PubMed  CAS  Google Scholar 

  329. Tong Q, Gamper N, Medina JL, Shapiro MS, Stockand JD (2004) Direct activation of the epithelial Na+ channel by phosphatidylinositol 3, 4, 5-trisphosphate and phosphatidylinositol 3, 4-bisphosphate produced by phosphoinositide 3-OH kinase. J Biol Chem 279:22654–22663

    PubMed  CAS  Google Scholar 

  330. Turnheim K (1991) Intrinsic regulation of apical sodium entry in epithelia. Physiol Rev 71:429–445

    PubMed  CAS  Google Scholar 

  331. Vallet V, Chraibi A, Gaeggeler HP, Horisberger JD, Rossier BC (1997) An epithelial serine protease activates the amiloride-sensitive sodium channel. Nature 389:607–610

    PubMed  CAS  Google Scholar 

  332. Vallet V, Pfister C, Loffing J, Rossier BC (2002) Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte. J Am Soc Nephrol 13:588–594

    PubMed  CAS  Google Scholar 

  333. Vaziri ND, Gonzales EC, Shayestehfar B, Barton CH (1994) Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome. J Lab Clin Med 124:118–124

    PubMed  CAS  Google Scholar 

  334. Verlander JW, Moudy RM, Campbell WG, Cain BD, Wingo CS (2001) Immunohistochemical localization of H-K-ATPase α2c-subunit in rabbit kidney. Am J Physiol Renal Physiol 281:F357–F365

    PubMed  CAS  Google Scholar 

  335. Verrey F (1994) Antidiuretic hormone action in A6 cells: effect on apical Cl and Na conductances and synergism with aldosterone for NaCl reabsorption. J Membr Biol 138:65–76

    PubMed  CAS  Google Scholar 

  336. Verrey F, Groscurth P, Bolliger U (1995) Cytoskeletal disruption in A6 kidney cells: impact on endo/exocytosis and NaCl transport regulation by antidiuretic hormone. J Membr Biol 145:193–204

    PubMed  CAS  Google Scholar 

  337. Verrey F, Hummler E, Schild L, Rossier BC (2007) Mineralocorticoid action in the aldosterone-sensitive distal nephron. In: Alpern RJ, Hebert SC (eds) Seldin and Giebisch’s the kidney. Elsevier, Amsterdam, pp 889–924

    Google Scholar 

  338. Verrey F, Fakitsas P, Adam G, Staub O (2008) Early transcriptional control of ENaC (de) ubiquitylation by aldosterone. Kidney Int 73:691–696

    PubMed  CAS  Google Scholar 

  339. Vettor R, Mazzonetto P, Macor C, Scandellari C, Federspil G (1994) Effect of endogenous organic hyperinsulinaemia on blood pressure and serum triglycerides. Eur J Clin Invest 24:350–354

    PubMed  CAS  Google Scholar 

  340. Vila-Carriles WH, Zhou ZH, Bubien JK, Fuller CM, Benos DJ (2007) Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells. J Biol Chem 282:34381–34391

    PubMed  CAS  Google Scholar 

  341. Vio CP, Figueroa CD (1987) Evidence for a stimulatory effect of high potassium diet on renal kallikrein. Kidney Int 31:1327–1334

    PubMed  CAS  Google Scholar 

  342. Volk T, Konstas AA, Bassalay P, Ehmke H, Korbmacher C (2004) Extracellular Na+ removal attenuates rundown of the epithelial Na+-channel (ENaC) by reducing the rate of channel retrieval. Pflugers Arch 447:884–894

    PubMed  CAS  Google Scholar 

  343. Vuagniaux G, Vallet V, Jaeger NF, Pfister C, Bens M, Farman N, Courtois-Coutry N, Vandewalle A, Rossier BC, Hummler E (2000) Activation of the amiloride-sensitive epithelial sodium channel by the serine protease mCAP1 expressed in a mouse cortical collecting duct cell line. J Am Soc Nephrol 11:828–834

    PubMed  CAS  Google Scholar 

  344. Vuagniaux G, Vallet V, Jaeger NF, Hummler E, Rossier BC (2002) Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus oocytes. J Gen Physiol 120:191–201

    PubMed  CAS  Google Scholar 

  345. Wagner CA, Devuyst O, Bourgeois S, Mohebbi N (2009) Regulated acid-base transport in the collecting duct. Pflugers Arch (in press)

  346. Wakida N, Kitamura K, Tuyen DG, Maekawa A, Miyoshi T, Adachi M, Shiraishi N, Ko T, Ha V, Nonoguchi H, Tomita K (2006) Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-beta1 and aldosterone. Kidney Int 70:1432–1438

    PubMed  CAS  Google Scholar 

  347. Waldmann R, Champigny G, Bassilana F, Voilley N, Lazdunski M (1995) Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel. J Biol Chem 270:27411–27414

    PubMed  CAS  Google Scholar 

  348. Wang J, Barbry P, Maiyar AC, Rozansky DJ, Bhargava A, Leong M, Firestone GL, Pearce D (2001) SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. Am J Physiol Renal Physiol 280:F303–F313

    PubMed  CAS  Google Scholar 

  349. Wang J, Zhang ZR, Chou CF, Liang YY, Gu Y, Ma HP (2009) Cyclosporine stimulates the renal epithelial sodium channel by elevating cholesterol. Am J Physiol Renal Physiol 296:F284–F290

    PubMed  CAS  Google Scholar 

  350. Wang SN, Lapage J, Hirschberg R (1999) Glomerular ultrafiltration of IGF-I may contribute to increased renal sodium retention in diabetic nephropathy. J Lab Clin Med 134:154–160

    PubMed  CAS  Google Scholar 

  351. Wang T, Giebisch G (1996) Effects of angiotensin II on electrolyte transport in the early and late distal tubule in rat kidney. Am J Physiol 271:F143–F149

    PubMed  CAS  Google Scholar 

  352. Wang WH, Giebisch G (2008) Regulation of potassium (K) handling in the renal collecting duct. Pflugers Arch (in press)

  353. Weisz OA, Wang JM, Edinger RS, Johnson JP (2000) Non-coordinate regulation of endogenous epithelial sodium channel (ENaC) subunit expression at the apical membrane of A6 cells in response to various transporting conditions. J Biol Chem 275:39886–39893

    PubMed  CAS  Google Scholar 

  354. West A, Blazer-Yost B (2005) Modulation of basal and peptide hormone-stimulated Na transport by membrane cholesterol content in the A6 epithelial cell line. Cell Physiol Biochem 16:263–270

    PubMed  CAS  Google Scholar 

  355. Wielputz MO, Lee IH, Dinudom A, Boulkroun S, Farman N, Cook DI, Korbmacher C, Rauh R (2007) (NDRG2) stimulates amiloride-sensitive Na+ currents in Xenopus laevis oocytes and fisher rat thyroid cells. J Biol Chem 282:28264–28273

    PubMed  Google Scholar 

  356. Wilson PD (1999) Cystic fibrosis transmembrane conductance regulator in the kidney: clues to its role? Exp Nephrol 7:284–289

    PubMed  CAS  Google Scholar 

  357. Woollhead AM, Scott JW, Hardie DG, Baines DL (2005) Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells. J Physiol 566:781–792

    PubMed  CAS  Google Scholar 

  358. Wulff P, Vallon V, Huang DY, Volkl H, Yu F, Richter K, Jansen M, Schlunz M, Klingel K, Loffing J, Kauselmann G, Bosl MR, Lang F, Kuhl D (2002) Impaired renal Na+ retention in the sgk1-knockout mouse. J Clin Invest 110:1263–1268

    PubMed  CAS  Google Scholar 

  359. Xu BE, Stippec S, Chu PY, Lazrak A, Li XJ, Lee BH, English JM, Ortega B, Huang CL, Cobb MH (2005) WNK1 activates SGK1 to regulate the epithelial sodium channel. Proc Natl Acad Sci U S A 102:10315–10320

    PubMed  CAS  Google Scholar 

  360. Xu BE, Stippec S, Lazrak A, Huang CL, Cobb MH (2005) WNK1 activates SGK1 by a phosphatidylinositol 3-kinase-dependent and non-catalytic mechanism. J Biol Chem 280:34218–34223

    PubMed  CAS  Google Scholar 

  361. Xu JZ, Hall AE, Peterson LN, Bienkowski MJ, Eessalu TE, Hebert SC (1997) Localization of the ROMK protein on apical membranes of rat kidney nephron segments. Am J Physiol 273:F739–F748

    PubMed  CAS  Google Scholar 

  362. Yagil C, Hubner N, Monti J, Schulz H, Sapojnikov M, Luft FC, Ganten D, Yagil Y (2005) Identification of hypertension-related genes through an integrated genomic-transcriptomic approach. Circ Res 96:617–625

    PubMed  CAS  Google Scholar 

  363. Yamamura H, Ugawa S, Ueda T, Nagao M, Shimada S (2004) Protons activate the delta-subunit of the epithelial Na+ channel in humans. J Biol Chem 279:12529–12534

    PubMed  CAS  Google Scholar 

  364. Yang LM, Rinke R, Korbmacher C (2006) 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 281:9859–9868

    PubMed  CAS  Google Scholar 

  365. Yu JX, Chao L, Chao J (1994) Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland. J Biol Chem 269:18843–18848

    PubMed  CAS  Google Scholar 

  366. Yue G, Malik B, Eaton DC (2002) Phosphatidylinositol 4, 5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells. J Biol Chem 277:11965–11969

    PubMed  CAS  Google Scholar 

  367. Zhai XY, Thomsen JS, Birn H, Kristoffersen IB, Andreasen A, Christensen EI (2006) Three-dimensional reconstruction of the mouse nephron. J Am Soc Nephrol 17:77–88

    PubMed  Google Scholar 

  368. Zhang W, Xia X, Reisenauer MR, Rieg T, Lang F, Kuhl D, Vallon V, Kone BC (2007) Aldosterone-induced Sgk1 relieves Dot1a-Af9-mediated transcriptional repression of epithelial Na+ channel alpha. J Clin Invest 117:773–783

    PubMed  CAS  Google Scholar 

  369. Zhang YH, Alvarez de la Rosa D, Canessa CM, Hayslett JP (2005) Insulin-induced phosphorylation of ENaC correlates with increased sodium channel function in A6 cells. Am J Physiol Cell Physiol 288:C141–C147

    PubMed  CAS  Google Scholar 

  370. Zhou Z, Treis D, Schubert SC, Harm M, Schatterny J, Hirtz S, Duerr J, Boucher RC, Mall MA (2008) Preventive but not late amiloride therapy reduces morbidity and mortality of lung disease in βENaC-overexpressing mice. Am J Respir Crit Care Med 178:1245–1256

    PubMed  CAS  Google Scholar 

  371. Zuber AM, Singer D, Penninger JM, Rossier BC, Firsov D (2007) Increased renal responsiveness to vasopressin and enhanced V2 receptor signaling in RGS2−/− mice. J Am Soc Nephrol 18:1672–1678

    PubMed  CAS  Google Scholar 

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Acknowledgements

Cited work of the authors’ laboratories was supported by grants from the Swiss National Science Foundation (to J.L.), the Cloëtta Foundation (to J.L), the Novartis Research Foundation (to J.L.), the Wellcome Trust (to. C.K.), the Deutsche Forschungsgemeinschaft (SFB 423: Kidney injury: Pathogenesis and regenerative mechanism; to C.K.), the Johannes und Frieda Marohn-Stiftung (to C.K.) and the Interdisciplinary Centre of Clinical Research (IZKF) of the University of Erlangen-Nürnberg (to C.K.).

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  1. Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

    Johannes Loffing

  2. Institut für Zelluläre und Molekulare Physiologie, Universität Erlangen-Nürnberg, Waldstr. 6, 91054, Erlangen, Germany

    Christoph Korbmacher

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  1. Johannes Loffing
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Correspondence to Johannes Loffing or Christoph Korbmacher.

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Loffing, J., Korbmacher, C. Regulated sodium transport in the renal connecting tubule (CNT) via the epithelial sodium channel (ENaC). Pflugers Arch - Eur J Physiol 458, 111–135 (2009). https://doi.org/10.1007/s00424-009-0656-0

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