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(Circulation Research. 2008;103:223.)
© 2008 American Heart Association, Inc.

Editorials

Calsequestrin Mutations and Sudden Death

A Case of Too Little Sarcoplasmic Reticulum Calcium Buffering?

Luigi A. Venetucci, David A. Eisner

From the Unit of Cardiac Physiology, University of Manchester, UK.

Correspondence to D. A. Eisner, Unit of Cardiac Physiology, University of Manchester, 3.18 Core Technology Facility, 46 Grafton St, Manchester M13 9NT, United Kingdom. E-mail eisner@man.ac.uk

See related article, pages 298–306

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
In cardiac muscle, calcium plays a crucial role in excitation–contraction coupling, but it is also implicated in arrhythmogenesis. Calcium is released from the sarcoplasmic reticulum (SR), resulting in the systolic Ca transient. This release occurs through a specialized channel, the ryanodine receptor (RyR). The RyR is formed by the assembly of 4 identical subunits and binds several accessory proteins that are involved in the control of its function. Channel opening is influenced by Ca levels on both the luminal and cytosolic side and the amount of Ca released depends steeply¹ on SR Ca content.

	Diastolic Calcium Release and Arrhythmias

 
In various conditions, the SR can release Ca independently from an action potential. This diastolic release propagates through the cell as a wave of calcium-induced calcium release. Some of the calcium is pumped out of the cell by the electrogenic Na–Ca exchange, resulting in delayed afterdepolarizations (DADs) and triggered arrhythmias (reviewed elsewhere²). Diastolic Ca release occurs when the SR Ca concentration reaches a critical, threshold level.³ Recent studies have suggested that DADs and arrhythmias can be produced not only as a consequence of elevated SR Ca content but also if the properties of Ca release from the SR are altered.

	Cathecholiminergic Polymorphic Ventricular Tachycardia

 
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic disorder characterized by the onset of ventricular tachycardia (VT) during stress. Two forms have been described, an autosomal dominant (CPVT-1) resulting from mutations of RyR^4,5 and an autosomal recessive (CPVT-2) resulting from mutations of calsequestrin (CSQ).⁶ Both animal⁷ and human⁸ studies have demonstrated that CPVT-1 arrhythmias . . . [Full Text of this Article]

Related Article:

Unexpected Structural and Functional Consequences of the R33Q Homozygous Mutation in Cardiac Calsequestrin: A Complex Arrhythmogenic Cascade in a Knock In Mouse Model

Nicoletta Rizzi, Nian Liu, Carlo Napolitano, Alessandra Nori, Federica Turcato, Barbara Colombi, Silvio Bicciato, Diego Arcelli, Alessandro Spedito, Mario Scelsi, Laura Villani, Giovanni Esposito, Simona Boncompagni, Feliciano Protasi, Pompeo Volpe, and Silvia G. Priori
Circ. Res. 2008 103: 298-306. [Abstract] [Full Text] [PDF]