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Arrhythmogenic Mechanism of a Novel Ryanodine Receptor Mutation Underlying Sudden Cardiac Death by Yunyun Qian; Dongchuan Zuo; Jing Xiong; Yihen Yin; Ruxi Qi; Xiaomin Ma; An Yan; Yawen Yang; Ping Liu; Jingying Zhang; Kai Tang; Wenhui Peng; Yawei Xu; Zheng Liu is a Medicine article available to read on EtoBox.
What is Arrhythmogenic Mechanism of a Novel Ryanodine Receptor Mutation Underlying Sudden Cardiac Death about?
## Abstract ## Aims The ryanodine receptor 2 (RyR2) is essential for cardiac muscle excitation–contraction coupling; dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we aimed to investigate the pathogenic basis of the mutation. ## Methods and results We generated a mouse model that carried the A690E mutation. Mice were characterized by adrenergic-induced ventricular arrhythmias similar to clinical manifestation of the patient. Optical mapping studies revealed that isolated A690E hearts were prone to arrhythmogenesis and displayed frequency-dependence calcium transient alternans. Upon β-adrenoceptor challenge, the concordant alternans was shifted towards discordant alternans that favour triggering ectopic beats and Ca^2+^ re-entry; similar phenomenon was also found in the A690E cardiomyocytes. In addition, we found that A690E cardiomyocytes manifested abnormal Ca^2+^ release and electrophysiological disorders, including an increased sensitivity to cytosolic Ca^2+^, an elevated diastolic RyR2-mediated Ca^2+^ leak,
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- Author
- Yunyun Qian; Dongchuan Zuo; Jing Xiong; Yihen Yin; Ruxi Qi; Xiaomin Ma; An Yan; Yawen Yang; Ping Liu; Jingying Zhang; Kai Tang; Wenhui Peng; Yawei Xu; Zheng Liu
- Publisher
- Oxford University Press (OUP)
- Published
- 2023
- Language
- EN
- Field
- Medicine (Health Sciences)