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

Authors

Qixin Yang
Hanna J Tadros
Bo Sun
Minu-Tshyeto Bidzimou
Jordan E Ezekian
Feng Li
Andreas Ludwig
Xander H T Wehrens
Andrew P Landstrom

Language

English

Publication Date

12-1-2023

Journal

JACC: Basic to Translational Science

DOI

10.1016/j.jacbts.2023.07.008

PMID

38205351

PMCID

PMC10774596

PubMedCentral® Posted Date

9-27-2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

calcium, JET, Jph2, junctional ectopic tachycardia, ryanodine receptor

Published Open-Access

yes

Recommended Citation

Yang, Qixin; Tadros, Hanna J; Sun, Bo; et al., "Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade" (2023). Faculty and Staff Publications. 4006.
https://digitalcommons.library.tmc.edu/baylor_docs/4006