THE EPITHELIAL SODIUM-CHANNEL - RECENT DEVELOPMENTS

Several types of amiloride-sensitive Na+ channels have been described in the apical membrane of tight epithelia. A highly Na+-selective, low -conductance type is found when transepithelial Na+ transport is stimu lated, while different types are observed under other conditions. The channel appears to be constituted of a large protein complex including several potential subunits. Recently, highly Na+-selective amiloride- sensitive channels have been expressed from a single cDNA clone isolat ed from rat colon. This cDNA probably encodes a pore-forming subunit. The predicted amino acid sequence includes two putative transmembrane segments and presents homology with genes expressed in specific neuron es of the nematode Caenorhabditis elegans. These genes are involved in touch sensory transduction and, when mutated, can cause neuronal cell death, probably by alteration of the membrane ionic permeability. Thi s indicates that the Na+ channel is part of a new family of cation cha nnels. The epithelial Na+ channel is regulated by hormonal and intrace llular factors. Aldosterone increases the open probability of channels present in the apical membrane and, in a late phase, induces the synt hesis and expression of new channel proteins. Vasopressin rapidly incr eases the number of channels present in the apical membrane, probably by translocation from a subapical channel pool. Evidence for regulatio n by G proteins, intracellular Ca2+, protein kinase C and interaction with the cytoskeleton are discussed.