Imaging atrial arrhythmic intracellular calcium in intact heart

Wenjun Xie, Gaetano Santulli, Xiaoxiao Guo, Melanie Gao, Bi Xing Chen, Andrew R. Marks

Research output: Contribution to journalArticle

47 Scopus citations

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 languageEnglish (US)
Pages (from-to)120-123
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume64
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

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Keywords

  • Atrial arrhythmias
  • Ex vivo model
  • Intracellular Ca imaging

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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