Complex Arrhythmia Syndrome in a Knock-In Mouse Model Carrier of the N98S <i>Calm1</i> Mutation

Abstract

Heterozygosity for the <i>Calm1</i>^N98S mutation is causative of an arrhythmia syndrome characterized by sinus bradycardia, QRS widening, adrenergically mediated QTc interval prolongation, and bidirectional ventricular tachycardia. β-Adrenergically induced <i>I</i>_Ca.L dysregulation contributes to the long-QT phenotype. Pause-dependent early afterdepolarizations and tachycardia-induced delayed afterdepolarizations originating in the His-Purkinje network and ventricular myocytes, respectively, constitute potential sources of arrhythmia in Calm1^N98S/+ hearts.