The RyR (ryanodine receptor) mediates rapid Ca2+ efflux from the ER (endoplasmic 
reticulum) and is responsible for triggering numerous Ca2+-activated 
physiological processes. The most studied RyR-mediated process is 
excitation-contraction coupling in striated muscle, where plasma membrane 
excitation is transmitted to the cell interior and results in Ca2+ efflux that 
triggers myocyte contraction. Recently, single-residue mutations in the cardiac 
RyR (RyR2) have been identified in families that exhibit CPVT (catecholaminergic 
polymorphic ventricular tachycardia), a condition in which physical or emotional 
stress can trigger severe tachyarrhythmias that can lead to sudden cardiac 
death. The RyR2 mutations in CPVT are clustered in the N- and C-terminal 
domains, as well as in a central domain. Further, a critical signalling role for 
dysfunctional RyR2 has also been implicated in the generation of arrhythmias in 
the common condition of HF (heart failure). We have prepared cardiac RyR2 
plasmids with various CPVT mutations to enable expression and analysis of Ca2+ 
release mediated by the wild-type and mutated RyR2. These studies suggest that 
the mutational locus may be important in the mechanism of Ca2+ channel 
dysfunction. Understanding the causes of aberrant Ca2+ release via RyR2 may 
assist in the development of effective treatments for the ventricular 
arrhythmias that often leads to sudden death in HF and in CPVT.