Structure and regulation of the amiloride-sensitive epithelial sodium channel.

Abstract

In high-resistance epithelia such as distal segments of the kidney tubule, distal colon, urinary bladder, skin, or airways, coupling of passive electrodiffusion of sodium through the apical membrane with active extrusion of intracellular sodium by Na+/K+/ATPases present in the basolateral membrane generates active Na+ reabsorption via a transcellular pathway (Palmer, 1992; Eaton and Hamilton, 1988; Garty and Benos, 1986). The rate-limiting factor for sodium reabsorption by the epithelial lining is formed by an apical Na+ channel that can be blocked by the diuretic molecules triamterene and amiloride (Eigler and Crabbe, 1969). Different hormones control the activity of this channel. For instance, aldosterone regulates the sodium balance, blood volume, and blood pressure by stimulating channel activity in kidney and in the distal colon (Garty and Benos, 1986; Rossier and Palmer, 1992); similarly, glucocorticoids increase the reabsorption of sodium in lung, thereby regulating the amount of respiratory fluid (O’Brodovich, 1991; Champigny et al., 1994). In these different tissues, the epithelial Na+ channel represents a major component of the total ionic permeability of the apical membrane.