AMILORIDE-SENSITIVE EPITHELIAL NA+ CHANNEL IS MADE OF 3 HOMOLOGOUS SUBUNITS

THE amiloride-sensitive epithelial sodium channel constitutes the rate -limiting step for sodium reabsorption in epithelial cells that line t he distal part of the renal tubule, the distal colon, the duct of seve ral exocrine glands, and the lung. The activity of this channel is upr egulated by vasopressin and aldosterone, hormones involved in the main tenance of sodium balance, blood volume and blood pressure1,2. We have identified the primary structure of the alpha-subunit of the rat epit helial sodium channel by expression cloning in Xenopus laevis oocytes3 . An identical subunit has recently been reported4. Here we identify t wo other subunits (beta and gamma) by functional complementation of th e alpha-subunit of the rat epithelial Na+ channel. The ion-selective p ermeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are s imilar to that of the native channel.