Mutations in ryanodine receptor 2 (RYR2) gene can cause catecholaminergic 
polymorphic ventricular tachycardia (CPVT). The novel RYR2-S4153R mutation has 
been implicated as a cause of CPVT and atrial fibrillation. The mutation has 
been functionally characterized via store-overload-induced Ca(2+) release 
(SOICR) and tritium-labelled ryanodine ([(3)H]ryanodine) binding assays. The 
S4153R mutation enhanced propensity for spontaneous Ca(2+) release and reduced 
SOICR threshold but did not alter Ca(2+) activation of [(3)H]ryanodine binding, 
a common feature of other CPVT gain-of-function RYR2 mutations. We conclude that 
the S4153R mutation is a gain-of-function RYR2 mutation associated with a 
clinical phenotype characterized by both CPVT and atrial fibrillation.