ENaC in the brain--future perspectives and pharmacological implications.

The epithelial sodium channel/degenerin (ENaC/deg) family of ion channels is formed by a large number of genes with variable tissue expression patterns and physiological roles. ENaC is a non-voltage gated, constitutively active channel highly selective for sodium. ENaC is formed by three homologous subunits, α, β and γ, and a fourth subunit (δ) has been found in human and monkeys that can substitute α to form functional channels. The best-characterized role of ENaC is to serve as a rate-limiting step in transepithelial sodium reabsorption in the distal part of the kidney tubule and other tight epithelia. However, ENaC subunits are also found in the peripheral and central nervous system, where their functional roles are only beginning to be understood. In this review, we mainly focus on the putative pathophysiological roles of ENaC channels in the central nervous system and their potential value as drug targets in neurodegenerative disorders and the central control of blood pressure.