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Paradoxical effect of increased diastolic Ca(2+) release and decreased sinoatrial node activity in a mouse model of catecholaminergic polymorphic ven…
2012
Background— Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored. Methods and Results— We investigated SAN [Ca 2+ ] i handling in mice carrying the catecholaminergic polymorphic ventricular tachycardia–linked mutation of ryanodine receptor (RyR2 R4496C ) and their wild-type (WT) littermates. In vivo telemetric recordings showed impaired SAN automaticity in RyR2 R4496C mice after isoproterenol injection, analogous to what was observed in catecholaminergic polymorphic ventricul…