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

Yang Q, Tadros HJ, Sun B, Bidzimou MT, Ezekian JE, Li F, Ludwig A, Wehrens XH, Landstrom AP (2023)

Publication Type: Journal article

Publication year: 2023

Journal

JACC: Basic To Translational Science American College of Cardiology

DOI: 10.1016/j.jacbts.2023.07.008

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.

Authors with CRIS profile

Andreas Ludwig Lehrstuhl für Pharmakologie und Toxikologie

Involved external institutions

Duke University US United States (USA) (US) Baylor College of Medicine US United States (USA) (US)

How to cite

APA:

Yang, Q., Tadros, H.J., Sun, B., Bidzimou, M.T., Ezekian, J.E., Li, F.,... Landstrom, A.P. (2023). Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade. JACC: Basic To Translational Science. https://doi.org/10.1016/j.jacbts.2023.07.008

MLA:

Yang, Qixin, et al. "Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade." JACC: Basic To Translational Science (2023).

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