Calcium‐mediated cellular triggered activity in atrial fibrillation. (22nd March 2017)

• Record Type: Journal Article
• Authors: Dobrev, Dobromir; Wehrens, Xander H. T.
• Is Part Of: Journal of physiology. Volume 595:Number 12(2017)
• Page Start: 4001
• Page End: 4008
• Publication Date: 2017-03-22
• Subjects: arrhythmia -- atrial fibrillation -- calcium -- ryanodine receptor -- triggered activity; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP273048
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Schematic diagram showing molecular mechanisms underlying abnormal SR Ca 2+ release associated with ectopic (triggered) activity in atrial fibrillation. Arrows indicate the direction of change. CaMKII, Ca 2+ /calmodulin‐dependent protein kinase II; NCX, Na + /Ca 2+ ‐exchanger; PKA, protein kinase A; PP1, protein phosphatase 1; RyR2, ryanodine receptor type‐2; SERCA2a, sarco/endoplasmic reticulum Ca 2+ ‐ATPase 2a. Abstract: Although atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, the basic mechanisms underlying this disorder remain incompletely understood. During the past decade or so, it has become clear that alterations in intracellular Ca 2+ handling may play a role in the pathogenesis of AF. Studies in small and large animal models, as well as atrial samples from patients with different forms of AF, have implicated ryanodine receptor type 2 (RyR2) dysfunction and enhanced spontaneous Ca 2+ release events from the sarcoplasmic reticulum (SR) as a potential cause of proarrhythmic cellular ectopic (triggered) activity in AF. The molecular mechanisms leading to RyR2 dysfunction and SR Ca 2+ leak depend on the clinical stage of AF or specific animal model studied. This review focuses on the mechanisms and role of calcium‐mediated cellular triggered activity in AF, and addresses some of the current controversies in the field.