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Calsequestrin Mutations and Catecholaminergic Polymorphic Ventricular Tachycardia

Abstract

Cardiac calsequestrin (Casq2) is the major Ca2+ binding protein in the sarcoplasmic reticulum, which is the principle Ca2+ storage organelle of cardiac muscle. During the last decade, experimental studies have provided new concepts on the role of Casq2 in the regulation of cardiac muscle Ca2+ handling. Furthermore, mutations in the gene encoding for cardiac calsequestrin, CASQ2, cause a rare but severe form of catecholaminergic polymorphic ventricular tachycardia (CPVT). Here, we review the physiology of Casq2 in cardiac Ca2+ handling and discuss pathophysiological mechanisms that lead to CPVT caused by CASQ2 mutations. We also describe the clinical aspects of CPVT and provide an update of its contemporary clinical management.

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Acknowledgments

This work was supported in part by United States National Institutes of Health Grants No. HL88635 and HL71670 (to B. C. K), by the American Heart Association Established Investigator Award 0840071 N (to B. C. K.), and by a Heart Rhythm Society Fellowship Award (to M. F.). We thank Frank Fish and Prince Kannankeril for providing the ECG examples as well as their editorial suggestions.

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None declared.

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Correspondence to Björn C. Knollmann.

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Faggioni, M., Kryshtal, D.O. & Knollmann, B.C. Calsequestrin Mutations and Catecholaminergic Polymorphic Ventricular Tachycardia. Pediatr Cardiol 33, 959–967 (2012). https://doi.org/10.1007/s00246-012-0256-1

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Keywords

  • Ventricular arrhythmia
  • Catecholaminergic polymorphic ventricular tachycardia
  • Calcium handling