Expression of the Epithelial NA⁺ Channel (ENAC) in Rat Kidney Colocalises with Aquaporin-2 (AQP-2)

Abstract

The apical surface of many tight epithelia express Na⁺-selective channels primarily characterized by the fact that they are selectively inhibited by submicromolar concentrations of the diuretic inhibitor amiloride (Garty and Palmer 1997). This channel is termed ENaC (epithelial Na⁺ channel) and belongs to the DEGenerin/ENaC gene super family. The members of this family are implicated in several cellular functions, including mechanosensation, proprioseption, pain sensation, gametogenesis and sodium transport (Mano et al., 1999). ENaC has been cloned from rat (Canessa et al., 1995), human (Mc. Donald et al., 1995) and other species. ENaC is composed of three homologous subunits α-, ß- and γ-ENaC. The three subunits share limited sequence similarity (∼30–40%), suggesting that they are derived from a common ancestral gene. The ENaC subunits have similar topologies with short intracellular NH₂ and COOH termini, two transmembrane domains, and a large cysteine rich extracellular loop. Putative functions for these regions have been obtained by analysing mutations found in genes coding for human ENaC subunits. The amiloride sensitivity and the selectivity of the channel has been shown to be dependent of a short segment proceeding the second membrane spanning domain suggesting an implication of this domain in the pore structure of ENaC (Schild et al, 1997). A gating domain was identified within the highly conserved N-terminus whereas a well-conserved PPxY motif in the C-terminus promotes interaction with intracellular proteins e.g. Nedd4 (Abriel et al, 1999) and proteins proteins in the clathrin mediated endocytic pathway (Shimkets et al, 1997).