Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8475024 | Journal of Molecular and Cellular Cardiology | 2013 | 12 Pages |
Abstract
Abnormalities in intracellular Ca2Â + signaling have been proposed to play an essential role in the pathophysiology of atrial arrhythmias. However, a direct observation of intracellular Ca2Â + in atrial myocytes during atrial arrhythmias is lacking. Here, we have developed an ex vivo model of simultaneous Ca2Â + imaging and electrocardiographic recording in cardiac atria. Using this system we were able to record atrial arrhythmic intracellular Ca2Â + activities. Our results indicate that atrial arrhythmias can be tightly linked to intracellular Ca2Â + waves and Ca2Â + alternans. Moreover, we applied this strategy to analyze Ca2Â + signals in the hearts of WT and knock-in mice harboring a 'leaky' type 2 ryanodine receptor (RyR2-R2474S). We showed that sarcoplasmic reticulum (SR) Ca2Â + leak increases the susceptibility to Ca2Â + alternans and Ca2Â + waves increasing the incidence of atrial arrhythmias. Reduction of SR Ca2Â + leak via RyR2 by acute treatment with S107 reduced both Ca2Â + alternans and Ca2Â + waves, and prevented atrial arrhythmias.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Wenjun Xie, Gaetano Santulli, Xiaoxiao Guo, Melanie Gao, Bi-Xing Chen, Andrew R. Marks,