Protection from cardiac arrhythmia through ryanodine receptor--stabilizing protein calstabin2

Ventricular arrhythmias can cause sudden cardiac death (SCD) in patients with normal hearts and in those with underlying disease such as heart failure. In animals with heart failure and in patients with inherited forms of exercise-induced SCD, depletion of the channel-stabilizing protein calstabin2 (FKBP12.6) from the ryanodine receptor-calcium release channel (RyR2) complex causes an intracellular [Ca.sup.2+] leak that can trigger fatal cardiac arrhythmias. A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the [Ca.sup.2+] leak that triggers arrhythmias. Thus, enhancing the binding of calstabin2 to RyR2 may be a therapeutic strategy for common ventricular arrhythmias.
Ventricular tachyarrhythmias that cause SCD are often associated with common heart diseases, such as heart failure, but may also occur in individuals without structural heart disease (1). Treatment remains largely [...]