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Sorcin ablation plus ?-adrenergic stimulation generate an arrhythmogenic substrate in mouse ventricular myocytes.


ABSTRACT: Sorcin, a penta-EF hand Ca2+-binding protein expressed in cardiomyocytes, is known to interact with ryanodine receptors and other Ca2+ regulatory proteins. To investigate sorcin's influence on cardiac excitation-contraction coupling and its role in the development of cardiac malfunctions, we generated a sorcin knockout (KO) mouse model. Sorcin KO mice presented ventricular arrhythmia and sudden death when challenged by acute stress induced by isoproterenol plus caffeine. Chronic stress, which was induced by transverse aortic constriction, significantly decreased the survival rate of sorcin KO mice. Under isoproterenol stimulation, spontaneous Ca2+ release events were frequently observed in sorcin KO cardiomyocytes. Sorcin KO hearts of adult, but not young mice developed overexpression of L-type Ca2+ channel and Na+-Ca2+ exchanger, which enhanced ICa and INCX. Consequently, spontaneous Ca2+ release events in sorcin KO cardiomyocytes were more likely to induce arrhythmogenic delayed afterdepolarizations. Our study demonstrates sorcin deficiency may trigger cardiac ventricular arrhythmias due to Ca2+ disturbances, and evidences the critical role of sorcin in maintaining Ca2+ homeostasis, especially during the adrenergic response of the heart.

SUBMITTER: Chen X 

PROVIDER: S-EPMC5800963 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Sorcin ablation plus β-adrenergic stimulation generate an arrhythmogenic substrate in mouse ventricular myocytes.

Chen Xi X   Weber Craig C   Farrell Emily T ET   Alvarado Francisco J FJ   Zhao Yan-Ting YT   Gómez Ana M AM   Valdivia Héctor H HH  

Journal of molecular and cellular cardiology 20171122


Sorcin, a penta-EF hand Ca<sup>2+</sup>-binding protein expressed in cardiomyocytes, is known to interact with ryanodine receptors and other Ca<sup>2+</sup> regulatory proteins. To investigate sorcin's influence on cardiac excitation-contraction coupling and its role in the development of cardiac malfunctions, we generated a sorcin knockout (KO) mouse model. Sorcin KO mice presented ventricular arrhythmia and sudden death when challenged by acute stress induced by isoproterenol plus caffeine. Ch  ...[more]

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