Inherited arrhythmias are the leading causes for cardiac arrest and sudden cardiac death (SCD). Other than ion channel mutations, inherited arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF) and arrhythmogenic right ventricular cardiomyopathy (ARVC/D) may also be instigated by genetic mutations of sarcoplasmic reticulum (SR) proteins, including ryanodine receptor type-2 (RyR2), calsequestrin 2, SR Ca2+-ATPase type-2a (SERCA2a) and phospholamban. In cardiomyocytes, Ca2+ is an essential ion in addition to Na+ and K+ ions with vital roles in arrhythmogenesis. SR plays a critical role in the maintenance of Ca2+ homeostasis which can be disrupted by mutations in SR Ca2+ regulatory proteins or abnormal SR-intracellular organelle interaction. Early afterdepolarizations, delayed afterdepolarizations and reentry are three primary mechanisms contributing to arrhythmias elicited by SR Ca2+ dysregulation in cardiomyocytes. In this review, we will aim to summarize normal SR Ca2+ regulation in cardiomyocytes, mechanisms of how Ca2+ triggers arrhythmias and involvements of SR gene mutations in inherited arrhythmias as well as the possible arrhythmogenic effects of these mutations.
Keywords: CPVT; Calcium; Inherited arrhythmias; LQTS; Ryanodine receptor; Sarcoplasmic reticulum.
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