EPITHELIAL SODIUM-CHANNELS - FUNCTION, STRUCTURE, AND REGULATION

The apical (outward-facing) membranes of high-resistance epithelia con tain Na+ channels, traditionally identified by their sensitivity to bl ock by the K+-sparing diuretic amiloride. Such channels have been char acterized in amphibian skin and urinary bladder, renal collecting duct , distal colon, sweat and salivary glands, lung, and taste buds. They mediate the first step of active Na+ reabsorption and play a major rol e in the maintenance of electrolyte and water homeostasis in all verte brates. In the past, these channels were classified according to their biophysical and pharmacological properties. The recent cloning of the three homologous channel subunits denoted alpha-, beta-, and gamma-ep ithelial Na+ channels (ENaC) has provided a molecular definition of at least one class of amiloride-blockable channels. Subsequent studies h ave established that ENaC is a major Na+-conducting pathway in both ab sorbing and secretory epithelia and is related to one type of channel involved in mechanosensation. This review summarizes the biophysical c haracteristics, molecular properties, and regulatory mechanisms of epi thelial amiloride-blockable Na+ channels. Special emphasis is given to recent studies utilizing cloned ENaC subunits and purified amiloride- binding proteins.