Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 64, Issue -, Pages 120-123Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2013.09.003
Keywords
Atrial arrhythmias; Intracellular Ca2+ imaging; Ex vivo model
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Funding
- AHA [13POST16810041]
- NIH [R01HL102040]
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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. (C) 2013 Elsevier Ltd. All rights reserved.
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