Ryanodine receptors (RyRs) are the calcium release channels of sarcoplasmic 
reticulum (SR) that provide the majority of calcium ions (Ca(2+)) necessary to 
induce contraction of cardiac and skeletal muscle cells. In their intracellular 
environment, RyR channels are regulated by a variety of cytosolic and luminal 
factors so that their output signal (Ca(2+)) induces finely-graded cell 
contraction without igniting cellular processes that may lead to aberrant 
electrical activity (ventricular arrhythmias) or cellular remodeling. The 
importance of RyR dysfunction has been recently highlighted with the 
demonstration that point mutations in RYR2, the gene encoding for the cardiac 
isoform of the RyR (RyR2), are associated with catecholaminergic polymorphic 
ventricular tachycardia (CPVT), an arrhythmogenic syndrome characterized by the 
development of adrenergically-mediated ventricular tachycardia in individuals 
with an apparently normal heart. Here we summarize the state of the field in 
regards to the main arrhythmogenic mechanisms triggered by RyR2 channels 
harboring mutations linked to CPVT. Most CPVT mutations characterized to date 
endow RyR2 channels with a gain of function, resulting in hyperactive channels 
that release Ca(2+) spontaneously, especially during diastole. The spontaneous 
Ca(2+) release is extruded by the electrogenic Na(+)/Ca(2+) exchanger, which 
depolarizes the external membrane (delayed afterdepolarization or DAD) and may 
trigger untimely action potentials. However, a rare set of CPVT mutations yield 
RyR2 channels that are intrinsically hypo-active and hypo-responsive to stimuli, 
and it is unclear whether these channels release Ca(2+) spontaneously during 
diastole. We discuss novel cellular mechanisms that appear more suitable to 
explain ventricular arrhythmias due to RyR2 loss-of-function mutations.