Can Novel Therapies for Arrhythmias Caused by Spontaneous Sarcoplasmic Reticulum Ca2 Release be Developed Using Mouse Models?

Ventricular arrhythmias are a significant cause ofpremature death in Western society and occur both inthe absence and presence of heart disease. For example, in heart failure close to 50 % of patients die of lethal forms of ventricular arrhythmias. In spite of a large amount of basic and clinical investigations, current pharmacotherapy for ventricular arrhythmias is inadequate, demonstrating the need for novel therapeutic approaches. Abnormal automaticity is responsible for induction and maintenance of different types of ventricular tachycardias. The form of abnormal automaticity that results from abnor-mal release of Ca2 from a Ca2 overloaded sarcoplasmic reticulum (SR), referred to as a “triggered arrhythmia”, is the topic of this editorial. In vitro studies have shown that increasing the SR Ca2 load beyond a critical level causes spontaneous opening of the SR Ca2 release channel (ryano-dine receptor; RYR) and results in spontaneous SR Ca