ABSTRACT
Acid-sensing ion channels (ASICs) are proton-gated cation channels expressed in sensory neurons and the central nervous system. ASICs sense fluctuations of extracellular proton concentrations arisen from neuronal activity and synaptic transmission but also pathological acidification from ischemia and inflammation. The ubiquitous presence of protons and wide distribution of ASICs in the brain enable ASICs to modulate a broad range of processes ranging from nociception to behaviors. Besides protons, endogenous neuropeptides (FMFRamide derivatives, dynorphin) and other molecules (arachidonic acid, polyamines, Zn2+) modulate ASIC activities. Also, toxins from venoms inhibit or activate ASICs, drawing interest as research tools and potential therapeutic agents. ASICs belong to a large family of ion channels known as ENaC/degenerin, a name given from the two founding channels. Members of this family vary in means of activation, but all share a common architecture that was elucidated solving the molecular structure of ASIC in various conformational states. The archetypical structure is a trimer with a distinctive pore formed by three split α-helices and the amino termini of each subunit entering the lower pore. Understanding of the physiology and structure ASIC has advanced greatly, yet more work is needed to unleash its potential as a target to treat neurological disorders.
