Cardiac excitation-contraction coupling occurs by a calcium ion-mediated 
mechanism in which the signal of action potential is converted into Ca2+ influx 
into the cardiomyocytes through the sarcolemmal L-type calcium channels. This is 
followed by Ca2+-induced release of additional Ca2+ ions from the lumen of the 
sarcoplasmic reticulum into the cytosol via type 2 ryanodine receptors (RyR2). 
RyR2 channels form large complexes with additional regulatory proteins, 
including FKBP12.6 and calsequestrin 2 (CASQ2). Catecholamines, released into 
the body fluids during emotional or physical stress, activate Ca2+-induced Ca2+ 
release by protein kinase A-mediated phosphorylation of RyR2. Catecholaminergic 
polymorphic ventricular tachycardia (CPVT) is an insidious, early-onset and 
highly malignant, inherited disorder characterized by effort-induced ventricular 
arrhythmias in the absence of structural alterations of the heart. At least some 
cases of sudden, unexplained death in young individuals may be ascribed to CPVT. 
Mutations of the RyR2 gene cause autosomal dominant CPVT, while mutations of the 
CASQ2 gene may cause an autosomal recessive or dominant form of CPVT. The steps 
of the molecular pathogenesis of CPVT are not entirely clear, but inappropriate 
"leakiness" of RyR2 channels is thought to play a role; the underlying 
mechanisms may involve an increase in the basal activity of the RyR2 channel, 
alterations in its phosphorylation status, a defective interaction of RyR2 with 
other molecules or ions, such as FKBP12.6, CASQ2, or Mg2+, or its abnormal 
activation by extra- or intraluminal Ca2+ ions. Beta-adrenergic antagonists have 
proven to be of value in prevention of arrhythmias in CPVT patients, but 
occasional treatment failures call for alternative measures. There is great 
interest at present for the development of novel antiarrhythmic drugs for CPVT, 
as the same approaches may be applied for treatment of more common forms of 
life-threatening arrhythmias, such as those arising during ischemia and heart 
failure.