RT Journal Article SR Electronic T1 International Union of Basic and Clinical Pharmacology. XCI. Structure, Function, and Pharmacology of Acid-Sensing Ion Channels and the Epithelial Na+ Channel JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 1 OP 35 DO 10.1124/pr.114.009225 VO 67 IS 1 A1 Stephan Kellenberger A1 Laurent Schild A2 Eliot H. Ohlstein YR 2015 UL http://pharmrev.aspetjournals.org/content/67/1/1.abstract AB The epithelial Na+ channel (ENaC) and the acid-sensing ion channels (ASICs) form subfamilies within the ENaC/degenerin family of Na+ channels. ENaC mediates transepithelial Na+ transport, thereby contributing to Na+ homeostasis and the maintenance of blood pressure and the airway surface liquid level. ASICs are H+-activated channels found in central and peripheral neurons, where their activation induces neuronal depolarization. ASICs are involved in pain sensation, the expression of fear, and neurodegeneration after ischemia, making them potentially interesting drug targets. This review summarizes the biophysical properties, cellular functions, and physiologic and pathologic roles of the ASIC and ENaC subfamilies. The analysis of the homologies between ENaC and ASICs and the relation between functional and structural information shows many parallels between these channels, suggesting that some mechanisms that control channel activity are shared between ASICs and ENaC. The available crystal structures and the discovery of animal toxins acting on ASICs provide a unique opportunity to address the molecular mechanisms of ENaC and ASIC function to identify novel strategies for the modulation of these channels by pharmacologic ligands.