Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance

J Clin Invest. 2003 Aug;112(4):554-65. doi: 10.1172/JCI16956.


Aldosterone controls the final sodium reabsorption and potassium secretion in the kidney by regulating the activity of the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN). ASDN consists of the last portion of the distal convoluted tubule (late DCT), the connecting tubule (CNT), and the collecting duct (CD) (i.e., the cortical CD [CCD] and the medullary CD [MCD]). It has been proposed that the control of sodium transport in the CCD is essential for achieving sodium and potassium balance. We have tested this hypothesis by inactivating the alpha subunit of ENaC in the CD but leaving ENaC expression in the late DCT and CNT intact. Under salt restriction or under aldosterone infusion, whole-cell voltage clamp of principal cells of CCD showed no detectable ENaC activity, whereas large amiloride-sensitive currents were observed in control littermates. The animals survive well and are able to maintain sodium and potassium balance, even when challenged by salt restriction, water deprivation, or potassium loading. We conclude that the expression of ENaC in the CD is not a prerequisite for achieving sodium and potassium balance in mice. This stresses the importance of more proximal nephron segments (late DCT/CNT) to achieve sodium and potassium balance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldosterone / blood
  • Animals
  • Electrophysiology
  • Epithelial Sodium Channels
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • Kidney Tubules / metabolism
  • Kidney Tubules / physiology*
  • Kidney Tubules, Collecting / metabolism
  • Kidney Tubules, Collecting / physiology*
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Potassium / metabolism
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Salts / metabolism
  • Sodium / metabolism
  • Sodium Channels / genetics*
  • Sodium Channels / physiology*
  • Time Factors
  • Water / metabolism


  • Epithelial Sodium Channels
  • Homeodomain Proteins
  • Hoxb7 protein, mouse
  • RNA, Messenger
  • Salts
  • Sodium Channels
  • Water
  • Aldosterone
  • Sodium
  • Potassium