RYR2 Channel Inhibition Is the Principal Mechanism of Flecainide Action in CPVT.

ABSTRACT:

Rationale

The class Ic antiarrhythmic drug flecainide prevents ventricular tachyarrhythmia in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease caused by hyperactive RyR2 (cardiac ryanodine receptor) mediated calcium (Ca) release. Although flecainide inhibits single RyR2 channels in vitro, reports have claimed that RyR2 inhibition by flecainide is not relevant for its mechanism of antiarrhythmic action and concluded that sodium channel block alone is responsible for flecainide's efficacy in CPVT.

Objective

To determine whether RyR2 block independently contributes to flecainide's efficacy for suppressing spontaneous sarcoplasmic reticulum Ca release and for preventing ventricular tachycardia in vivo.

Methods and results

We synthesize

SUBMITTER: Kryshtal DO 

PROVIDER: S-EPMC7864884 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature