Abstract
Abnormalities in intracellular Ca2+ signaling have been proposed to play an essential role in the pathophysiology of atrial arrhythmias. However, a direct observation of intracellular Ca2+ in atrial myocytes during atrial arrhythmias is lacking. Here, we have developed an ex vivo model of simultaneous Ca2+ imaging and electrocardiographic recording in cardiac atria. Using this system we were able to record atrial arrhythmic intracellular Ca2+ activities. Our results indicate that atrial arrhythmias can be tightly linked to intracellular Ca2+ waves and Ca2+ alternans. Moreover, we applied this strategy to analyze Ca2+ 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) Ca2+ leak increases the susceptibility to Ca2+ alternans and Ca2+ waves increasing the incidence of atrial arrhythmias. Reduction of SR Ca2+ leak via RyR2 by acute treatment with S107 reduced both Ca2+ alternans and Ca2+ waves, and prevented atrial arrhythmias.
Original language | English (US) |
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Pages (from-to) | 120-123 |
Number of pages | 4 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 64 |
DOIs | |
State | Published - Nov 2013 |
Externally published | Yes |
Keywords
- Atrial arrhythmias
- Ex vivo model
- Intracellular Ca imaging
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine