title: Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation.
abstract: Extracellular acidification occurs not only in pathological conditions such as inflammation and brain ischemia, but also in normal physiological conditions such as synaptic transmission. Acid-sensing ion channels (ASICs) can detect a broad range of physiological pH changes during pathological and synaptic cellular activities. ASICs are voltage-independent, proton-gated cation channels widely expressed throughout the central and peripheral nervous system. Activation of ASICs is involved in pain perception, synaptic plasticity, learning and memory, fear, ischemic neuronal injury, seizure termination, neuronal degeneration, and mechanosensation. Therefore, ASICs emerge as potential therapeutic targets for manipulating pain and neurological diseases. The activity of these channels can be regulated by many factors such as lactate, Zn(2+), and Phe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides by interacting with the channel's large extracellular loop. ASICs are also modulated by G protein-coupled receptors such as CB1 cannabinoid receptors and 5-HT2. This review focuses on the physiological roles of ASICs and the molecular mechanisms by which these channels are regulated.
authors.affiliation: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.
authors.forename: Hae-Jin
authors.initials: HJ
authors.lastname: Kweon
authors.forename: Byung-Chang
authors.initials: BC
authors.lastname: Suh
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000737:chemistry / Q000627:therapeutic use; D062565:Acid Sensing Ion Channels / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D043562:Receptors, G-Protein-Coupled