title: Impaired epithelial Na+ channel activity contributes to cystogenesis and development of autosomal recessive polycystic kidney disease in PCK rats.
abstract: BACKGROUND
  Autosomal recessive polycystic kidney disease is a genetic disorder characterized by the development of renal cysts of tubular epithelial cell origin. Epithelial Na(+) channel (ENaC) is responsible for sodium reabsorption in the aldosterone-sensitive distal nephron. Here, we investigated the ENaC expression and activity in cystic tissue taken from rats with autosomal recessive polycystic kidney disease.
  
  
  METHODS
  Polycystic kidney (PCK) rats were treated with the selective ENaC inhibitor benzamil given in the drinking water, and after 4 or 12 wk, the severity of morphological malformations in the kidneys was assessed. ENaC and aquaporin-2 expression and ENaC activity were tested with immunohistochemistry and patch-clamp electrophysiology, respectively.
  
  
  RESULTS
  Treatment with benzamil exacerbated development of cysts compared with the vehicle-treated animals. In contrast, the 12 wk of treatment with the loop diuretic furosemide had no effect on cystogenesis. Single-channel patch-clamp analysis revealed that ENaC activity in the freshly isolated cystic epithelium was significantly lower than that in the noncystic collecting ducts isolated from PCK or normal Sprague-Dawley rats. Immunohistochemical analysis confirmed that β-ENaC and aquaporin-2 expressions in cysts are decreased compared with nondilated tubules from PCK rat kidneys.
  
  
  CONCLUSIONS
  We demonstrated that cystic epithelium exhibits low ENaC activity and this phenomenon can contribute to cyst progression.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tengis S
authors.initials: TS
authors.lastname: Pavlov
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Levchenko
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Ilatovskaya
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Alexander
authors.identifier: 0000000251908356
authors.initials: A
authors.lastname: Staruschenko
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017044:Polycystic Kidney, Autosomal Recessive / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000737:chemistry*
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D053503:Epithelial Sodium Channels; C013407:benzamil; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium