The epithelial sodium channel δ-subunit: new notes for an old song

Abstract

Amiloride-sensitive epithelial Na(+) channels (ENaCs) can be formed by different combinations of four homologous subunits, named α, β, γ, and δ. In addition to providing an apical entry pathway for transepithelial Na(+) reabsorption in tight epithelia such as the kidney distal tubule and collecting duct, ENaCs are also expressed in nonepithelial cells, where they may play different functional roles. The δ-subunit of ENaC was originally identified in humans and is able to form amiloride-sensitive Na(+) channels alone or in combination with β and γ, generally resembling the canonical kidney ENaC formed by α, β, and γ. However, δ differs from α in its tissue distribution and channel properties. Despite the low sequence conservation between α and δ (37% identity), their similar functional characteristics provide an excellent model for exploring structural correlates of specific ENaC biophysical and pharmacological properties. Moreover, the study of cellular mechanisms modulating the activity of different ENaC subunit combinations provides an opportunity to gain insight into the regulation of the channel. In this review, we examine the evolution of ENaC genes, channel subunit composition, the distinct functional and pharmacological features that δ confers to ENaC, and how this can be exploited to better understand this ion channel. Finally, we briefly consider possible functional roles of the ENaC δ-subunit.

Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction

“…Thus impairment of the Na-K-ATPase during ALI not only prevents resolution of pulmonary edema but also exacerbates its formation. Recently, a fourth subunit of ENaC, termed ␦ ENaC, was discovered and proved to have unique biophysical and pharmacological properties compared with ␣ ENaC (76,112). Importantly, in human primary nasal epithelial cells (humans express ␦ ENaC) up to 40% of amiloride-sensitive sodium transport is associated with ␦ ENaC (9), and alterations in nasal potential may be indicative of Na ϩ channel dysfunction in ALI (146).…”

Expression and function of the epithelial sodium channel δ-subunit in human respiratory epithelial cells in vitro

“…Because the molecular basis for the distinct sodium conductances detected in native respiratory epithelial cells has not been identified, the possible contribution of δ-ENaC-generated currents to the net sodium transport is of a particular interest. However, the fact that δ-ENaC in rodents is a pseudogene hinders the development of experimental animal models, thus in vitro approaches are currently the most promising to elucidate the physiological function of the ion channel [21].…”

Elevated Expression of the Delta-Subunit of Epithelial Sodium Channel in Temporal Lobe Epilepsy Patients and Rat Model

“…It has four subunits: α ENaC, β ENaC, γ ENaC, and δ ENaC. It has been reported that the most prominently expressed ENaC subunit in the human brain cortex is δ, while very low expression levels of α, β, and γ have been detected (Waldmann et al 1995;Yamamura et al 2004;Giraldez et al 2007Giraldez et al , 2012. Additionally, expression of δ ENaC is restricted to neurons (Giraldez et al 2007).…”