title: Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels.
abstract: Acid-sensing ion channels (ASICs) are voltage-independent proton-gated cation channels that are largely expressed in the nervous system as well as in some non-neuronal tissues. In rodents, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) can associate into homo- or hetero-trimers to form a functional channel. Specific polypeptide toxins targeting ASIC channels have been isolated from the venoms of spider (PcTx1), sea anemone (APETx2) and snakes (MitTx and mambalgins). They exhibit different and sometimes partially overlapping pharmacological profiles and are usually blockers of ASIC channels, except for MitTx, which is a potent activator. This review focuses on the use of these toxins to explore the structure-function relationships, the physiological and the pathophysiological roles of ASIC channels, illustrating at the same time the therapeutic potential of some of these natural compounds.
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, 06560 Valbonne, France; Université de Nice-Sophia Antipolis, 06560 Valbonne, France; LabEx Ion Channel Science and Therapeutics, 06560 Valbonne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Baron
authors.forename: Sylvie
authors.initials: S
authors.lastname: Diochot
authors.forename: Miguel
authors.initials: M
authors.lastname: Salinas
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Deval
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.forename: Eric
authors.initials: E
authors.lastname: Lingueglia
mesh_terms: D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000595:Amino Acid Sequence; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D012377:Rodentia; D012615:Sea Anemones; D012911:Snakes; D013112:Spiders; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000302:isolation & purification / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014688:Venoms / Q000737:chemistry*
chemical_list: D062565:Acid Sensing Ion Channels; D014151:Anti-Anxiety Agents; D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D018696:Neuroprotective Agents; D010455:Peptides; D014118:Toxins, Biological; D014688:Venoms
keywords: ASIC; Nervous system; Pain; Pathophysiology; Sodium channels; Toxins