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J Mol Cell Cardiol. 2013 Nov;64:120-3. doi: 10.1016/j.yjmcc.2013.09.003. Epub 2013 Sep 13.

Imaging atrial arrhythmic intracellular calcium in intact heart.

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Helen and Clyde Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.


Abnormalities in intracellular Ca(2+) signaling have been proposed to play an essential role in the pathophysiology of atrial arrhythmias. However, a direct observation of intracellular Ca(2+) in atrial myocytes during atrial arrhythmias is lacking. Here, we have developed an ex vivo model of simultaneous Ca(2+) imaging and electrocardiographic recording in cardiac atria. Using this system we were able to record atrial arrhythmic intracellular Ca(2+) activities. Our results indicate that atrial arrhythmias can be tightly linked to intracellular Ca(2+) waves and Ca(2+) alternans. Moreover, we applied this strategy to analyze Ca(2+) 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) Ca(2+) leak increases the susceptibility to Ca(2+) alternans and Ca(2+) waves increasing the incidence of atrial arrhythmias. Reduction of SR Ca(2+) leak via RyR2 by acute treatment with S107 reduced both Ca(2+) alternans and Ca(2+) waves, and prevented atrial arrhythmias.


Atrial arrhythmias; Ex vivo model; Intracellular Ca(2+) imaging

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