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BIBTEX RIS

Human induced pluripotent stem cell-derived atrial cardiomyocytes carrying an SCN5A mutation identify nitric oxide signaling as a mediator of atrial fibrillation

2021; Elsevier BV; Volume: 16; Issue: 6 Linguagem: Inglês

10.1016/j.stemcr.2021.04.019

ISSN

2213-6711

Autores

Liang Hong, Meihong Zhang, Olivia T Ly, Hanna Chen, Arvind Sridhar, Erin Lambers, Brandon Chalazan, Seock‐Won Youn, Mark Maienschein‐Cline, Leonid Feferman, Sang‐Ging Ong, Joseph C. Wu, Jalees Rehman, Dawood Darbar,

Tópico(s)

Cardiac Arrhythmias and Treatments

Resumo

Mutations in SCN5A, encoding the cardiac sodium channel, are linked with familial atrial fibrillation (AF) but the underlying pathophysiologic mechanisms and implications for therapy remain unclear. To characterize the pathogenesis of AF-linked SCN5A mutations, we generated patient-specific induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) from two kindreds carrying SCN5A mutations (E428K and N470K) and isogenic controls using CRISPR-Cas9 gene editing. We showed that mutant AF iPSC-aCMs exhibited spontaneous arrhythmogenic activity with beat-to-beat irregularity, prolonged action potential duration, and triggered-like beats. Single-cell recording revealed enhanced late sodium currents (I

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