دورية أكاديمية
Calcium Signaling Consequences of RyR2-S4938F Mutation Expressed in Human iPSC-Derived Cardiomyocytes
العنوان: | Calcium Signaling Consequences of RyR2-S4938F Mutation Expressed in Human iPSC-Derived Cardiomyocytes |
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المؤلفون: | Noemi Toth, Xiao-Hua Zhang, Alexandra Zamaro, Martin Morad |
المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 20, p 15307 (2023) |
بيانات النشر: | MDPI AG, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | S4938F mutation, RyR2 Ca2+ signaling, CRISPR/Cas9, CICR, Ca2+ spark, Ca2+ release deficiency, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Type-2 ryanodine receptor (RyR2) is the major Ca2+ release channel of the cardiac sarcoplasmic reticulum (SR) that controls the rhythm and strength of the heartbeat, but its malfunction may generate severe arrhythmia leading to sudden cardiac death or heart failure. S4938F-RyR2 mutation in the carboxyl-terminal was expressed in human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) using CRISPR/Cas9 gene-editing technique. Ca2+ signaling and electrophysiological properties of beating cardiomyocytes carrying the mutation were studied using total internal reflection fluorescence microscopy (TIRF) and patch clamp technique. In mutant cells, L-type Ca2+ currents (ICa), measured either by depolarizations to zero mV or repolarizations from +100 mV to –50 mV, and their activated Ca2+ transients were significantly smaller, despite their larger caffeine-triggered Ca2+ release signals compared to wild type (WT) cells, suggesting ICa-induced Ca2+ release (CICR) was compromised. The larger SR Ca2+ content of S4938F-RyR2 cells may underlie the higher frequency of spontaneously occurring Ca2+ sparks and Ca2+ transients and their arrhythmogenic phenotype. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/24/20/15307; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms242015307 |
URL الوصول: | https://doaj.org/article/d302f351fea840db817a32ed2b60fb2b |
رقم الأكسشن: | edsdoj.302f351fea840db817a32ed2b60fb2b |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14220067 16616596 |
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DOI: | 10.3390/ijms242015307 |