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Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass

This highly cited paper describes an entirely new antiarrhythmic mechanism, which underlies the ability of flecainide to prevent life threatening exercise-induced arrhythmias in patients with the inherited condition ‘catecolaminergic polymorphic tachycardia’ (CPVT). The mechanism involves selective inhibition of intracellular Ca2+ release channel (ryanodine receptor: RyR2) in its open state, which abbreviates localised Ca2+ release events, thereby abolishing pro-arrhythmic Ca2+ waves. The discovery opens up a new direction for drug development and broader application to other causes of arrhythmia. In recognition of the significance of this finding, the paper was supported by an Editorial.