Aarhus Universitet

Birgitte Mønster Christensen

Sodium and potassium balance depends on αENaC expression in connecting tubule

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Birgitte Mønster Christensen
  • Romain Perrier
  • ,
  • Qing Wang
  • ,
  • Annie Mercier Zuber
  • ,
  • Marc Maillard
  • ,
  • David Mordasini
  • ,
  • Sumedha Malsure
  • ,
  • Caroline Ronzaud
  • ,
  • Jean-Christophe Stehle
  • ,
  • Bernard C Rossier
  • ,
  • Edith Hummler
  • Anatomisk Institut
Mutations in α, β, or γ subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans. In contrast, mice with selective inactivation of αENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis. To investigate the relative importance of ENaC-mediated sodium absorption in the CNT, we used Cre-lox technology to generate mice lacking αENaC in the aquaporin 2-expressing CNT and CD. Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of αENaC in the CCD and weak αENaC expression in the CNT. These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice. Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice. With dietary sodium restriction, these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia. Plasma aldosterone levels were significantly elevated under both standard and sodium-restricted diets. In summary, αENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing.
OriginalsprogEngelsk
TidsskriftJournal of the American Society of Nephrology
Vol/bind21
Nummer11
Sider (fra-til)1942-51
ISSN1046-6673
DOI
StatusUdgivet - 2010

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