title: Calmodulin kinase and L-type calcium channels; a recipe for arrhythmias?
abstract: L-type Ca2+ channels (LTCCs) are the main portal for Ca2+ entry into cardiac myocytes. These ion channel proteins open in response to cell membrane depolarizations elicited by action potentials, and LTCC current (I(Ca)) flows during the action potential plateau, to increase cellular Ca2+ (Ca2+(i)) and trigger myocardial contraction. I(Ca) is also implicated in the genesis of cardiac arrhythmias under conditions such as heart failure and cardiac hypertrophy, in which the action potential plateau and QT interval are prolonged. This article reviews recent findings about the molecular regulation of LTCCs by the Ca2+-dependent signaling molecule, calmodulin kinase II (CaMKII), and compares this form of regulation with regulation by calmodulin-binding domains and beta-adrenergic receptor agonists. LTCC dysregulation is discussed in the context of new results showing that CaMKII can be a proarrhythmic signal in disease conditions in which Ca2+(i) is disordered and cardiac repolarization is excessively prolonged.
authors.affiliation: Division of Cardiovascular Medicine, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, 383 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232-6300, USA. mark.anderson@vanderbilt.edu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Anderson
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D006801:Humans; D009200:Myocardial Contraction
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases