dc.contributor.author | Şahoğlu Göktaş, Sevilay | |
dc.contributor.author | Kazcı, Yusuf Enes | |
dc.contributor.author | Tuncay, Erkan | |
dc.contributor.author | Torun, Tuğçe | |
dc.contributor.author | Akdeniz, Celal | |
dc.contributor.author | Tuzcu, Volkan | |
dc.contributor.author | Çağavi, Esra | |
dc.date.accessioned | 2022-11-22T11:16:23Z | |
dc.date.available | 2022-11-22T11:16:23Z | |
dc.date.issued | 2022 | en_US |
dc.identifier.citation | Şahoğlu Göktaş, S., Kazcı, Y. E., Tuncay, E., Torun, T., Akdeniz, C., Tuzcu, V. ... Çağavi, E. (2022). Functional evaluation of the tachycardia patient-derived iPSC cardiomyocytes carrying a novel pathogenic SCN5A variant. Journal of Cellular Physiology, 237(10), 3900-3911. https://doi.org/10.1002/jcp.30843 | en_US |
dc.identifier.issn | 0021-9541 | |
dc.identifier.issn | 1097-4652 | |
dc.identifier.uri | https://doi.org/10.1002/jcp.30843 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12511/10009 | |
dc.description.abstract | Tachycardia is characterized by high beating rates that can lead to life-threatening fibrillations. Mutations in several ion-channel genes were implicated with tachycardia; however, the complex genetic contributors and their modes of action are still unclear. Here, we investigated the influence of an SCN5A gene variant on tachycardia phenotype by deriving patient-specific iPSCs and cardiomyocytes (iPSC-CM). Two tachycardia patients were genetically analyzed and revealed to inherit a heterozygous p.F1465L variant in the SCN5A gene. Gene expression and immunocytochemical analysis in iPSC-CMs generated from patients did not show any significant changes in mRNA levels of SCN5A or gross NaV1.5 cellular mislocalization, compared to healthy-derived iPSC-CMs. Electrophysiological and contraction imaging analysis in patient iPSC-CMs revealed intermittent fibrillation-like states, occasional arrhythmic events, and sustained high-paced contractions that could be selectively reduced by flecainide treatment. The patch-clamp analysis demonstrated a negative shift in the voltage-dependent activation at the patient-derived iPSC-CMs compared to the healthy control line, suggestive of a gain-of-function activity associated with the SCN5A(+/p.F1465L) variant. Our patient-derived iPSC-CM model recapitulated the clinically relevant characteristics of tachycardia associated with a novel pathogenic SCN5A(+/p.F1465L) variant leading to altered Na+ channel kinetics as the likely mechanism underlying high excitability and tachycardia phenotype. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Wiley | en_US |
dc.rights | info:eu-repo/semantics/embargoedAccess | en_US |
dc.subject | Cardiovascular Diseases | en_US |
dc.subject | In Vitro Disease Model | en_US |
dc.subject | IPSC | en_US |
dc.subject | SCN5A Variant | en_US |
dc.subject | Tachycardia | en_US |
dc.title | Functional evaluation of the tachycardia patient-derived iPSC cardiomyocytes carrying a novel pathogenic SCN5A variant | en_US |
dc.type | article | en_US |
dc.relation.ispartof | Journal of Cellular Physiology | en_US |
dc.department | İstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü | en_US |
dc.department | İstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Sinirbilim Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbi Biyoloji ve Genetik Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı | en_US |
dc.authorid | 0000-0002-8647-6055 | en_US |
dc.authorid | 0000-0001-9008-4997 | en_US |
dc.authorid | 0000-0002-7199-583X | en_US |
dc.identifier.volume | 237 | en_US |
dc.identifier.issue | 10 | en_US |
dc.identifier.startpage | 3900 | en_US |
dc.identifier.endpage | 3911 | en_US |
dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/213S192 | |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.1002/jcp.30843 | en_US |
dc.institutionauthor | Şahoğlu Göktaş, Sevilay | |
dc.institutionauthor | Kazcı, Yusuf Enes | |
dc.institutionauthor | Torun, Tuğçe | |
dc.institutionauthor | Akdeniz, Celal | |
dc.institutionauthor | Tuzcu, Volkan | |
dc.institutionauthor | Çağavi, Esra | |
dc.identifier.wosquality | Q1 | en_US |
dc.identifier.wos | 000839564000001 | en_US |
dc.identifier.scopus | 2-s2.0-85135855979 | en_US |
dc.identifier.pmid | 35959596 | en_US |
dc.identifier.scopusquality | Q1 | en_US |