Treatment of catecholaminergic polymorphic ventricular tachycardia in mice using novel RyR2-modifying drugs.

ABSTRACT:

Rationale

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal arrhythmic disorder caused by mutations in the type-2 ryanodine receptor (RyR2). Mutant RyR2 cause abnormal Ca²⁺ leak from the sarcoplasmic reticulum (SR), which is associated with the development of arrhythmias.

Objective

To determine whether derivatives of tetracaine, a local anesthetic drug with known RyR2 inhibiting action, could prevent CPVT induction by suppression of RyR2-mediated SR Ca²⁺ leak.

Methods and results

Confocal microscopy was used to assess the effects of tetracaine and 9 derivatives (EL1-EL9) on spontaneous Ca²⁺ sparks in ventricular myocytes isolated from RyR2-R176Q/+ mice with CPVT. Whereas each derivative suppressed the

SUBMITTER: Li N 

PROVIDER: S-EPMC5164850 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature