Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors.
The epithelial sodium channel (ENaC) expressed in aldosterone-responsive epithelial cells of the kidney and colon plays a critical role in the control of sodium balance, blood volume, and blood pressure. In lung, ENaC has a distinct role in controlling the ionic composition of the air-liquid interface and thus the rate of mucociliary transport. Loss-of-function mutations in ENaC cause a severe salt-wasting syndrome in human pseudohypoaldosteronism type 1 (PHA-1). Gain-of-function mutations in ENaC beta and gamma subunits cause pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive hypertension. This review discusses genetically defined forms of a salt sensitivity and salt resistance in human monogenic diseases and in animal models mimicking PHA-1 or Liddle's syndrome. The complex interaction between genetic factors (ENaC mutations) and the risk factor (salt intake) can now be studied experimentally. The role of single-nucleotide polymorphisms (SNPs) in determining salt sensitivity or salt resistance in general populations is one of the main challenges of the post-genomic era.
Rossier
Bernard C
BC
Institute of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, Lausanne, CH-1005 Switzerland. Bernard.Rossier@ipharm.unil.ch
Pradervand
Sylvain
S
Schild
Laurent
L
Hummler
Edith
E
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D053503:Epithelial Sodium Channels; D015633:Extravascular Lung Water / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*
D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human; D015222:Sodium Channels; D000450:Aldosterone; D012964:Sodium