Arrhythmogenesis in Catecholaminergic Polymorphic Ventricular Tachycardia
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- 4 August 2006
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 99 (3) , 292-298
- https://doi.org/10.1161/01.res.0000235869.50747.e1
Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulation; (2) decreased affinity of mutant RyR2 for FKBP12.6 causes CPVT; (3) K201 prevent arrhythmias by normalizing the FKBP12.6-RyR2 binding. We studied ventricular myocytes isolated from wild-type (WT) and knock-in mice harboring the R4496C mutation (RyR2R4496C+/−). Pacing protocols did not elicit delayed afterdepolarizations (DADs) (n=20) in WT but induced DADs in 21 of 33 (63%) RyR2R4496C+/− myocytes (P=0.001). Superfusion with isoproterenol (30 nmol/L) induced small DADs (45%) and no triggered activity in WT myocytes, whereas it elicited DADs in 87% and triggered activity in 60% of RyR2R4496C+/− myocytes (P=0.001). DADs and triggered activity were abolished by ryanodine (10 μmol/L) but not ...Keywords
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