title: Sodium channels as macromolecular complexes: implications for inherited arrhythmia syndromes.
abstract: Mutations in cardiac ion channels and their auxiliary subunits can lead to life-threatening cardiac arrhythmias. In recent years it has become apparent that ion channels are part of large, multi-protein complexes, comprising not only the ion channels and their auxiliary subunits, but also components of the cytoskeleton, regulatory kinases and phosphatases, trafficking proteins, extracellular matrix proteins, and possibly even other ion channels. Disruption of any member of a particular ion channel complex has the potential to disrupt the function of the associated channels, resulting in paroxysmal disease. Understanding the molecular composition of individual ion channel signaling complexes in heart may yield important insights into the molecular basis of cardiac arrhythmias and may suggest novel therapeutic approaches to treatment of these life-threatening conditions.
authors.affiliation: Department of Pharmacology, The University of Michigan, 1301 MSRB III, Box 0632, 1150 W. Medical Center Dr. Ann Arbor, MI 48109-0632, United States.
authors.forename: L S
authors.initials: LS
authors.lastname: Meadows
authors.forename: L L
authors.initials: LL
authors.lastname: Isom
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D049029:Dystrophin-Associated Proteins / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000378:metabolism; D046911:Macromolecular Substances / Q000378:metabolism*; D008869:Microtubule-Associated Proteins; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D017487:Ankyrins; D000889:Anti-Arrhythmia Agents; D049029:Dystrophin-Associated Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; C477056:NAV1 protein, human; D009414:Nerve Growth Factors; D019837:Ryanodine Receptor Calcium Release Channel; C091824:syntrophin