title: Imaging atrial arrhythmic intracellular calcium in intact heart.
abstract: 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.
authors.affiliation: 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.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xie
authors.forename: Gaetano
authors.initials: G
authors.lastname: Santulli
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Guo
authors.forename: Melanie
authors.initials: M
authors.lastname: Gao
authors.forename: Bi-Xing
authors.initials: BX
authors.lastname: Chen
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Marks
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004195:Disease Models, Animal; D004562:Electrocardiography; D006325:Heart Atria / Q000378:metabolism* / Q000503:physiopathology*; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D054802:Molecular Imprinting / Q000379:methods; D032383:Myocytes, Cardiac / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium
keywords: Atrial arrhythmias; Ex vivo model; Intracellular Ca(2+) imaging
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