Molecular biology of lung Na+ absorption

Abstract

A transcellular sodium reabsorption through high-resistance epithelia: couples passive electrodiffusion of sodium through the apical membrane, and active extrusion of intracellular sodium by basolateral Na+/K+/ATPase, and generates a vectorial transcellular sodium transport. In lung, this mechanism participates to the correct hydration of the luminal compartment. The apical electrodiffusion, which corresponds to the limiting step of transcellular transport, is mediated by an ionic channel, highly selective for sodium and lithium over potassium. This channel is blocked by the diuretics amiloride and triamterene. Molecular identification of the proteins involved in amiloride-sensitive sodium permeation has been achieved. Three homologous subunits, entitled αENaC, βENaC, and γENaC (for epithelial Na+ channel), correspond to the pore-forming subunits. They are distinct from voltage-dependent Na+ channels. Instead, they constitute with more than 20 homologous proteins, a new gene super-family of ionic channels. This family can be divided into three main subfamilies: (1) channels involved in vectorial transport of electrolytes, such as ENaC; (2) degenerins from Caenorhabditis elegans, such as DEG-1, MEC-4, MEC-10, UNC-8 and UNC-105, which are likely to correspond to mechanosensitive channels; (3) ligand-gated channels, such as FaNaC (for FMRFamide Na+ channel), an ionotropic receptor for the cardioexcitatory peptide Phe-Met-Arg-Phe-NH2 (FMRFamide) found in Helix aspersa nervous system, or ASIC (for acid sensing ionic channel), a mammalian H+-gated channel selective for monovalent and divalent cations. The physiological importance of the epithelial Na+ channel is highlighted by identification of mutations into aENaC, pENaC, and γENaC genes in families affected by pseudohypoaldosteronism type I (PHA1) or hereditary low-renin hypertension (Liddle’s syndrome).