title: International Union of Basic and Clinical Pharmacology. XCI. structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel.
abstract: 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.
authors.affiliation: Département de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland Stephan.Kellenberger@unil.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kellenberger
authors.affiliation: Département de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schild
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology*; D062565:Acid Sensing Ion Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology*; D053503:Epithelial Sodium Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects*; D008024:Ligands; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D008024:Ligands; D012964:Sodium