Chapter 13 - Epithelial Na+ channel

Abstract

The amiloride-sensitive epithelial sodium channel (ENaC) mediates the transport of sodium across the apical membranes of epithelial cells. It serves as the limiting step for Na+ reabsorption from the kidney distal tubule, the distal colon and the ducts of several exocrine glands. In a man, mutations in ENaC can result in hereditary hypertension or hypotension. ENaC is also involved in taste perception, regulates fluid secretion and absorption in the lung and controls the low Na+ concentration of the endolymph in the cochlea of the ear. The transport of Na+ across epithelia requires two proteins: (1) a Na+ uptake protein located on the apical membrane, and (2) the Na/K-ATPase, which resides in the basolateral membrane. These two proteins work together. In some epithelia, such as those of the distal tubule, Na+ enters the cell passively through ENaC channels in the luminal membrane. It is then extruded across the basolateral membrane by the activity of the Na/K-ATPase, which provides the driving force for the movement of Na across the cell. K+ entering the cell via the Na/K-ATPase leaves via one of many types of K1 channels and transporters. Electrophysiological studies suggest that there may be a family of amiloride-sensitive Na channels in epithelial tissues that can be distinguished, by their sensitivity to amiloride, selectivity to Na and single-channel conductance. Only the classical type of channel called “ ENaC,” is considered in the chapter. It is important to remember, however, that other kinds of amiloride-sensitive channels do exist. ENaC has a family of subunits; ENaC belongs to a family of related Ion channels with diverse functions, chromosomal location. The correlating structure and function of ENaC is studied in depth in this chapter. Finally, diseases associated with ENaC channels, such as disease of blood pressure regulation, Liddle's syndrome, pseudohypoaldosteronism Type-1, respiratory diseases in newborn, cystic fibrosis, and neuronal degeneration are also covered.