Urinary concentrating defect in mice lacking Epac1 or Epac2

Alena Cherezova, Viktor Tomilin, Vadym Buncha, Oleg Zaika, Pablo A. Ortiz, Fang Mei, Xiaodong Cheng, Mykola Mamenko, Oleh Pochynyuk

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


cAMPis a universal secondmessenger regulating a plethora of processes in the kidney.Twodownstream effectors of cAMP are PKA and exchange protein directly activated by cAMP (Epac), which, unlike PKA, is often linked to elevation of [Ca2+]i.While both Epac isoforms (Epac1 and Epac2) are expressed along the nephron, their relevance in the kidney remains obscure. We combined ratiometric calcium imaging with quantitative immunoblotting, immunofluorescent confocalmicroscopy, and balance studies inmice lacking Epac1 or Epac2 to determine the role of Epac in renal water-solute handling. Epac12/2 and Epac22/2 mice developed polyuria despite elevated arginine vasopressin levels.We did not detect major deficiencies in arginine vasopressin [Ca2+]i signaling in splitopened collecting ducts or decreases inaquaporinwater channel type 2 levels. Instead, sodium-hydrogenexchanger type 3 levels in the proximal tubule were dramatically reduced in Epac12/2 and Epac22/2 mice.Water deprivation revealed persisting polyuria, impaired urinary concentration ability, and augmented urinary excretion of Na+ and urea in bothmutant mice. In summary, we report a nonredundant contribution of Epac isoforms to renal function. Deletion of Epac1 and Epac2 decreases sodium-hydrogen exchanger type 3 expression in the proximal tubule, leading to polyuria and osmotic dieresis.

Original languageEnglish (US)
Pages (from-to)2156-2170
Number of pages15
JournalFASEB Journal
Issue number2
StatePublished - 2019


  • AQP2
  • Collecting duct
  • NHE-3
  • Urea
  • Water deprivation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Urinary concentrating defect in mice lacking Epac1 or Epac2'. Together they form a unique fingerprint.

Cite this