1.A.6.1.1
Epithelial Na⁺ channel, ENaC (regulates salt and fluid homeostasis and blood pressure; regulated by Nedd4 isoforms and SGK1, 2 and 3 kinases) (Henry et al., 2003; Pao 2012).  Cd²⁺ inhibits α-ENaC by binding to the internal pore where it interacts with residues in TMS2 (Takeda et al., 2007).  The channel is regulated by palmitoylation of the beta subunit which modulates gating (Mueller et al. 2010). ENaCs are more selective for Naa+ over other cations than ASICs (Yang and Palmer 2018). ENaC plays a role in chronic obstructive pulmonary diseases (COPD) (Zhao et al. 2014). The hetrodimeric complex can consist of αβγ or δβγ subunits, depending on the tissue (Giraldez et al. 2012).  The α- and γ-subunits of the epithelial Na⁺ channel interact directly with the Na⁺:Cl^- cotransporter, NCC, in the renal distal tubule with functional cosequences, and together they determine bodily salt balance and blood pressure (Mistry et al. 2016).  ENaC is regulated by syntaxins (Saxena et al. 2006). The cryoEM structure has been solved (Noreng et al. 2018). Interactions between the epithelial sodium channel gamma-subunit and claudin-8 modulates paracellular sodium permeability in the renal collecting duct (Sassi et al. 2020). Tumer necrosis factor, TNF, of 233 aas, is the source of a modified cyclic peptide of 17 aas, solnatide or the TIP peptide, (CGQRETPEGAEAKPWYC), residues 177 - 195), that activates ENaC (Madaio et al. 2019; Martin-Malpartida et al. 2022). Acid-Sensing ion channels are inhibited by KB-R7943, a reverse Na⁺/Ca²⁺ exchanger (see TC# 1.D.208) (Sun et al. 2023).  EGR-1 contributes to pulmonary edema by regulating the epithelial sodium channel in lipopolysaccharide-induced acute lung injury (Wang et al. 2023).  Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension (Tuineau et al. 2024).