EL20, a potent antiarrhythmic compound, selectively inhibits calmodulin-deficient ryanodine receptor type 2.

ABSTRACT:

Background

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disorder caused by mutations in the cardiac ryanodine receptor RyR2 that increase diastolic calcium cation (Ca²⁺) leak from the sarcoplasmic reticulum (SR). Calmodulin (CaM) dissociation from RyR2 has been associated with diastolic Ca²⁺ leak in heart failure.

Objective

Determine whether the tetracaine-derivative compound EL20 inhibits abnormal Ca²⁺ release from RyR2 in a CPVT model and investigate the underlying mechanism of inhibition.

Methods

Spontaneous Ca²⁺ sparks in cardiomyocytes and inducible ventricular tachycardia were assessed in a CPVT mouse model, which is heterozygous for the R176Q mutation in RyR2 (R176Q/+ mice) in the

SUBMITTER: Klipp RC 

PROVIDER: S-EPMC5879004 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature