Molecular properties of epithelial, amiloride-blockable Na+ channels

The apical membrane of many tight epithelia contains Na+ channels that are primarily characterized by their high affinity to the diuretic blocker amiloride. These channels mediate the first step of active Na+ reabsorption essential for the maintenance of body salt and water homeostasis. They are regulated by mineralocorticoids, antidiuretic peptides, atrial natriuretic peptides, and other factors. The molecular events that mediate the hormonal actions are poorly understood. In addition, patch clamp studies have established that amiloride-sensitive channels in different epithelia may differ in their regulatory mechanisms and biophysical properties. Several groups have reported the biochemical purification and/or molecular cloning of putative channel components. Of particular importance is the recent cloning of three cDNAs, whose coexpression in Xenopus oocytes evokes a large amiloride-blockable Na+ specific conductance (Canesa et al. (1994) Nature (London), 367, 463-467. This review summarizes existing data on properties, regulatory mechanisms, and diversity of amiloride-blockable channels, describes the different putative channel components identified, and examines possible relationships among them.