title: Calmodulin kinase II, sarcoplasmic reticulum Ca2+ leak, and atrial fibrillation.
abstract: Although it is generally accepted that excitation-contraction coupling is defective in patients with atrial fibrillation, the underlying cellular mechanisms remain incompletely understood. Recent studies suggest that abnormal sarcoplasmic reticulum calcium "leak" via ryanodine receptors contributes to atrial arrhythmogenesis. Increased activity of the enzyme calmodulin kinase II (CaMKII) and, specifically, enhanced CaMKII phosphorylation of ryanodine receptors appear to play a critical role in the induction and perhaps maintenance of atrial fibrillation. In this review, we will summarize new insights into the role of enhanced CaMKII in sarcoplasmic reticulum calcium leak and atrial arrhythmogenesis during atrial fibrillation.
authors.affiliation: Department of Pharmacology and Toxicology, Dresden University of Technology, Germany. dobrev@rcs.urz.tu-dresden.de
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation; D056966:Excitation Contraction Coupling / Q000187:drug effects; D006325:Heart Atria / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000889:Anti-Arrhythmia Agents; D047428:Protein Kinase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium