Reversal of convention: from man to experimental animal in elucidating the function of the renal amiloride-sensitive sodium channel.
The kidney plays a dominant role in maintaining sodium homeostasis. Despite wide variation in environmental exposure, the osmolality of the extracellular fluid that is determined by the sodium ion concentration is maintained within narrow margins. Derangement in function of proteins that transport Na+ and of those regulating the activity of these sodium-transporting proteins are likely to be responsible for a number of clinical disorders of fluid and electrolyte homeostasis. The amiloride-sensitive epithelial sodium channel (ENaC) is implicated in the control of blood pressure as demonstrated by the analysis of two genetic diseases, Liddle's syndrome and pseudohypoaldosteronism (PHA-1). Mutations have been identified in the genes coding for the alpha-, beta- or gamma-subunit of ENaC. ENaC constitutes the limiting step for sodium reabsorption in epithelial cells that line the distal nephron, distal colon, ducts of several exocrine glands and lung airways and might play an important role in pathophysiological and clinical conditions such as hypertension or lung edema.
Hummler
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Institut de Pharmacologie et de Toxicologie de l'Université, Lausanne, Switzerland. Edith.HummlerBeermann@ipharm.unil.ch
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D018390:Gene Targeting; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*
D015222:Sodium Channels; D000584:Amiloride