Inositol 1,4,5-Trisphosphate Receptor 1 Gain-of-Function Increases the Risk for Cardiac Arrhythmias in Mice and Humans

Ca2+ mishandling in cardiac Purkinje cells is a well-known cause of cardiac arrhythmias. The Purkinje cell resident inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is believed to play an important role in Ca2+ handling, and ITPR1 gain-of-function (GOF) has been implicated in cardiac arrhythmias. How...

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Detalhes bibliográficos
Autores: Sun, Bo, Ni, Mingke, Li, Yanhui, Song, Zhenpeng, Wang, Hui, Zhu, Hai-Lei, Wei, Jinhong, Belke, Darrell, Cai, Shitian, Guo, Wenting, Yao, Jinjing, Tian, Shanshan, Estillore, John Paul, Wang, Ruiwu, Søndergaard, Mads Toft, Brohus, Malene, Rohde, Palle Duun, Mu, Yongxin, Vallmitjana, Alexander, Benitez, Raul, Hove-Madsen, Leif, Overgaard, Michael Toft, Fishman, Glenn I., Chen, Ju, Sanatani, Shubhayan, Wilde, Arthur A. M., Fill, Michael, Ramos-Franco, Josefina, Nyegaard, Mette, Chen, S. R. Wayne
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/390901
Acesso em linha:http://hdl.handle.net/10261/390901
https://api.elsevier.com/content/abstract/scopus_id/105001364487
Access Level:acceso abierto
Palavra-chave:Purkinje cells
cardiac ryanodine receptor
inositol 1,4,5-trisphosphate receptor
sarcoplasmic reticulum
spontaneous Ca2+ release
ventricular arrhythmias
triggered activity
Descrição
Resumo:Ca2+ mishandling in cardiac Purkinje cells is a well-known cause of cardiac arrhythmias. The Purkinje cell resident inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is believed to play an important role in Ca2+ handling, and ITPR1 gain-of-function (GOF) has been implicated in cardiac arrhythmias. However, nearly all known disease-associated ITPR1 variants are loss-of-function and are primarily linked to neurological disorders. Whether ITPR1 GOF has pathological consequences, such as cardiac arrhythmias, is unclear. This study aimed to identify human ITPR1 GOF variants and determine the impact of ITPR1 GOF on Ca2+ handling and arrhythmia susceptibility.

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