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Molecular and Electrophysiological Bases of Catecholaminergic Polymorphic Ventricular Tachycardia
Author(s) -
MOHAMED UWAIS,
NAPOLITANO CARLO,
PRIORI SILVIA G.
Publication year - 2007
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2007.00766.x
Subject(s) - catecholaminergic polymorphic ventricular tachycardia , ryanodine receptor 2 , calsequestrin , ryanodine receptor , medicine , afterdepolarization , catecholaminergic , ventricular tachycardia , cardiology , genetics , electrophysiology , biology , calcium , dopamine , repolarization
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by adrenergically mediated polymorphic ventricular tachyarrhythmias. Genetic investigations have identified two variants of the disease: an autosomal dominant form associated with mutations in the gene encoding the cardiac ryanodine receptor (RyR2) and a recessive form associated with homozygous mutations in the gene encoding the cardiac isoform of calsequestrin (CASQ2). Functional characterization of mutations identified in the RyR2 and CASQ2 genes has demonstrated that CPVT are caused by derangements of the control of intracellular calcium. Investigations in a knock‐in mouse model have shown that CPVT arrhythmias are initiated by delayed afterdepolarizations and triggered activity. In the present article, we review clinical and molecular understanding of CPVT and discuss the most recent approaches to develop novel therapeutic strategies for the disease.