title: Role of sodium and calcium dysregulation in tachyarrhythmias in sudden cardiac death.
abstract: Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger, and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin-dependent protein kinase and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachyarrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like heart failure.
authors.affiliation: From the Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany (S.W., L.S.M.); and Department of Pharmacology, University of California, Davis, CA (D.M.B.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.affiliation: From the Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany (S.W., L.S.M.); and Department of Pharmacology, University of California, Davis, CA (D.M.B.). lars.maier@ukr.de.
authors.forename: Lars S
authors.initials: LS
authors.lastname: Maier
authors.affiliation: From the Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany (S.W., L.S.M.); and Department of Pharmacology, University of California, Davis, CA (D.M.B.).
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
mesh_terms: D000200:Action Potentials; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D004562:Electrocardiography; D044127:Epigenesis, Genetic; D056966:Excitation Contraction Coupling; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013610:Tachycardia / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D017180:Tachycardia, Ventricular / Q000378:metabolism; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D015220:Calcium Channels; D002317:Cardiovascular Agents; D015222:Sodium Channels; D012964:Sodium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: alternans; arrhythmias; calcium; calcium/calmodulin–dependent kinase II; sodium