Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade.
JACC Basic Transl Sci
; 8(12): 1577-1588, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-38205351
ABSTRACT
Junctional ectopic tachycardia (JET) is a potentially fatal cardiac arrhythmia. Hcn4shJph2 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, Hcn4shJph2 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.
Texto completo:
1
Banco de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
JACC Basic Transl Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos