Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade.

ABSTRACT: Junctional ectopic tachycardia (JET) is a potentially fatal cardiac arrhythmia. Hcn4:shJph2 mice serve as a model of nodal arrhythmias driven by ryanodine type 2 receptor (RyR2)-mediated Ca²⁺ leak. EL20 is a small molecule that blocks RyR2 Ca²⁺ leak. In a novel in vivo model of JET, Hcn4:shJph2 mice demonstrated rapid conversion of JET to sinus rhythm with infusion of EL20. Primary atrioventricular nodal cells demonstrated increased Ca²⁺ transient oscillation frequency and increased RyR2-mediated stored Ca²⁺ leak which was normalized by EL20. EL20 was found to be rapidly degraded in mouse and human plasma, making it a potential novel therapy for JET.

SUBMITTER: Yang Q 

PROVIDER: S-EPMC10774596 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature