title: Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.
abstract: The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electric impulse. Emerging evidence over the past 20 years strongly suggests that the normal electric function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, post-translational modification, turnover, function, and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium, and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electric function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy.
authors.affiliation: From the Department of Clinical Research, University of Bern, Bern, Switzerland (H.A., J.-S.R.); Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor (J.J.); and Area of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.J.).
authors.forename: Hugues
authors.initials: H
authors.lastname: Abriel
authors.affiliation: From the Department of Clinical Research, University of Bern, Bern, Switzerland (H.A., J.-S.R.); Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor (J.J.); and Area of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.J.).
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Rougier
authors.affiliation: From the Department of Clinical Research, University of Bern, Bern, Switzerland (H.A., J.-S.R.); Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor (J.J.); and Area of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.J.). jjalife@umich.edu.
authors.forename: José
authors.initials: J
authors.lastname: Jalife
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000502:physiology; D002451:Cell Compartmentation; D053447:Channelopathies / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D054086:KATP Channels / Q000737:chemistry / Q000502:physiology; D046911:Macromolecular Substances / Q000737:chemistry*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000502:physiology; D025941:Protein Interaction Mapping; D021122:Protein Subunits
chemical_list: D020746:Calcium Channels, L-Type; D007473:Ion Channels; D054086:KATP Channels; C489457:KCNJ2 protein, human; C419385:L-type calcium channel alpha(1C); D046911:Macromolecular Substances; D008565:Membrane Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; C568320:SCN5A protein, human
keywords: arrhythmias, cardiac; death, sudden, cardiac; ion channels; multiprotein complexes