Li, Wener and Stauske, Michael and Luo, Xiaojing and Wagner, Stefan and Vollrath, Meike and Mehnert, Carola S. and Schubert, Mario and Cyganek, Lukas and Chen, Simin and Hasheminasab, Sayed-Mohammad and Wulf, Gerald and El-Armouche, Ali and Maier, Lars S. and Hasenfuss, Gerd and Guan, Kaomei (2020) Disease Phenotypes and Mechanisms of iPSC-Derived Cardiomyocytes From Brugada Syndrome Patients With a Loss-of-Function SCN5A Mutation. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 8: 592893. ISSN 2296-634X,
Full text not available from this repository. (Request a copy)Abstract
Brugada syndrome (BrS) is one of the major causes of sudden cardiac death in young people, while the underlying mechanisms are not completely understood. Here, we investigated the pathophysiological phenotypes and mechanisms using induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) from two BrS patients (BrS-CMs) carrying a heterozygous SCN5A mutation p.S1812X. Compared to CMs derived from healthy controls (Ctrl-CMs), BrS-CMs displayed a 50% reduction of I-Na density, a 69.5% reduction of Na(V)1.5 expression, and the impaired localization of Na(V)1.5 and connexin 43 (Cx43) at the cell surface. BrS-CMs exhibited reduced action potential (AP) upstroke velocity and conduction slowing. The I-to in BrS-CMs was significantly augmented, and the I-CaL window current probability was increased. Our data indicate that the electrophysiological mechanisms underlying arrhythmia in BrS-CMs may involve both depolarization and repolarization disorders. Cilostazol and milrinone showed dramatic inhibitions of I-to in BrS-CMs and alleviated the arrhythmic activity, suggesting their therapeutic potential for BrS patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSIENT OUTWARD CURRENT; PLURIPOTENT STEM-CELLS; LONG-QT SYNDROME; EARLY REPOLARIZATION; SODIUM CURRENT; ANKYRIN-G; EXPRESSION; CILOSTAZOL; TRANSCRIPTION; FIBRILLATION; Brugada syndrome; disease modeling; induced pluripotent stem cells; SCN5A mutation; depolarization; repolarization |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 11:50 |
| Last Modified: | 08 Mar 2021 11:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43524 |
Actions (login required)
 |
View Item |
