The Amiloride-Sensitive Na + Channel: From Primary Structure to Function

Three homologous subunits of the amiloride-sensitive Na + channel, entitled α, β, and γ, have been cloned either from distal colon of a steroid-treated rat or from human lung. The α, β, and γ subunits have similarities with degenerins, a family of proteins found in the mechanosensory neurons of the nematode Caenorhabditis elegans. All these proteins are characterized by the presence of a large extracellular domain, located between two transmembrane α -helices, and by short NH 2 and COOH terminal cytoplasmic segments. They constitute the first members of a new gene super-family of ionic channels. The epithelial Na + channel is specifically expressed at the apical membrane of Na + -reabsorbing epithelial cells. Its activity is controlled by several distinct hormones, especially by corticosteroids. These hormones act either transcriptionally (such as aldosterone in distal colon, or glucocorticoids in lung) and/or post-transcriptionally (such as aldosterone in kidney). Recent works have provided new insights in the function of that important osmoregulatory system.