Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8473621 | Journal of Molecular and Cellular Cardiology | 2018 | 12 Pages |
Abstract
Sorcin, a penta-EF hand Ca2Â +-binding protein expressed in cardiomyocytes, is known to interact with ryanodine receptors and other Ca2Â + 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 Ca2Â + release events were frequently observed in sorcin KO cardiomyocytes. Sorcin KO hearts of adult, but not young mice developed overexpression of L-type Ca2Â + channel and Na+-Ca2Â + exchanger, which enhanced ICa and INCX. Consequently, spontaneous Ca2Â + 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 Ca2Â + disturbances, and evidences the critical role of sorcin in maintaining Ca2Â + homeostasis, especially during the adrenergic response of the heart.
Keywords
EADFDHMSorcinryanodine receptor type 2L-type Ca2 + channelBVTLTCCCPVTNCXRyR2EGTATACDAD1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acidE-C couplingethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acidPremature ventricular contractionearly afterdepolarizationBAPTAVentricular tachycardiaBidirectional ventricular tachycardiaCatecholaminergic polymorphic ventricular tachycardiaExcitation-contraction couplingtransverse aortic constrictionSarcoplasmic reticulumSERCASodium-calcium exchangerVentricular myocytesaction potentialdelayed afterdepolarizationPVCRyanodine receptors
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Authors
Xi Chen, Craig Weber, Emily T. Farrell, Francisco J. Alvarado, Yan-Ting Zhao, Ana M. Gómez, Héctor H. Valdivia,