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Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade.
Yang, Qixin; Tadros, Hanna J; Sun, Bo; Bidzimou, Minu-Tshyeto; Ezekian, Jordan E; Li, Feng; Ludwig, Andreas; Wehrens, Xander H T; Landstrom, Andrew P.
Afiliación
  • Yang Q; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
  • Tadros HJ; Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
  • Sun B; Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
  • Bidzimou MT; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
  • Ezekian JE; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
  • Li F; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
  • Ludwig A; Center for Drug Discovery and Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
  • Wehrens XHT; Institut für Experimentelle und Klinische Pharmakologie, und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Landstrom AP; Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
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.
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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
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

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