Amiloride-sensitive epithelial sodium channels constitute the rate-limiting step for sodium reabsorption in the distal part of the renal tubule, in the distal colon, in the ducts of several exocrine glands, and in the airways (Rossier et al., 1994). Until recently, the classification of the epithelial sodium channels was exclusively based on biophysical and pharmacological properties: sodium and potassium selectivity, single channel conductance, kinetics of gating and amiloride sensitivity. As recently pointed out by Garty and Palmer (1997), the molecular cloning of the three homologous channel subunits denoted α, β, and γ epithelial sodium channels (ENaC) has provided a molecular definition of at least one class of amiloride-blockable channels.

ENaC is the major sodium-conducting pathway in the distal nephron, participating in the fine control of sodium balance, blood volume, and blood pressure. ENaC also has a unique role in controlling lung fluid clearance, especially at birth (...

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