Catecholaminergic polymorphic ventricular tachycardia

The control of calcium fluxes in the heart is a key function that affects both excitability and contractility. At least two components of this pathway can generate inherited arrhythmias syndromes the release of calcium from its intracellular store, the sarcoplasmic reticulum and the transmembrane flux of calcium controlled by voltage-gated calcium channels. This chapter deals with inherited arrhythmias due to genetic defects of the proteins controlling sarcoplasmic reticulum calcium release, namely the catecholaminergic polymorphic ventricular tachycardia (CPVT). Two proteins, ryanodine receptor (RyR2) and calsequestrin (CASQ2) have been involved in the patogenesis of CPVT, a disorder characterized by adrenergically mediated bidirectional and/or polymorphic VT a structurally normal heart. The clinical presentation encompasses exercise-or emotion-induced syncopal spells and a distinctive pattern of reproducible, stress-related, bidirectional VT in the absence of structural heart disease. This chapter provides an overview of the structural organization and the function of calcium releasing proteins. We also describe the current understanding of the pathways leading form mutations to the clinical phenotype, which, in several cases, has driven (or it is driving) the development of more effective therapies.