Universität zu Köln

Kamga, Michelle Vanessa Kapchoup, Reppel, Michael, Hescheler, Jurgen and Nguemo, Filomain ORCID: 0000-0002-2236-6797 (2021). Modeling genetic cardiac channelopathies using induced pluripotent stem cells - Status quo from an electrophysiological perspective. Biochem. Pharmacol., 192. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 1873-2968

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Abstract

Long QT syndrome (LQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT) are genetic diseases of the heart caused by mutations in specific cardiac ion channels and are characterized by paroxysmal arrhythmias, which can deteriorate into ventricular fibrillation. In LQTS3 and BrS different mutations in the SCN5A gene lead to a gain-or a loss-of-function of the voltage-gated sodium channel Nav1.5, respectively. Although sharing the same gene mutation, these syndromes are characterized by different clinical manifestations and functional perturbations and in some cases even present an overlapping clinical phenotype. Several studies have shown that Na(+ )current abnormalities in LQTS3 and BrS can also cause Ca2+-signaling aberrancies in cardiomyocytes (CMs). Abnormal Ca2+ homeostasis is also the main feature of CPVT which is mostly caused by heterozygous mutations in the RyR2 gene. Large numbers of disease-causing mutations were identified in RyR2 and SCN5A but it is not clear how different variants in the SCN5A gene produce different clinical syndromes and if in CPVT Ca2+ abnormalities and drug sensitivities vary depending on the mutation site in the RyR2. These questions can now be addressed by using patient-specific in vitro models of these diseases based on induced pluripotent stem cells (iPSCs). In this review, we summarize different insights gained from these models with a focus on electrophysiological perturbations caused by different ion channel mutations and discuss how will this knowledge help develop better stratification and more efficient personalized therapies for these patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kamga, Michelle Vanessa Kapchoup UNSPECIFIED UNSPECIFIED UNSPECIFIED Reppel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED orcid.org/0000-0002-2236-6797 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-563088
DOI:	10.1016/j.bcp.2021.114746
Journal or Publication Title:	Biochem. Pharmacol.
Volume:	192
Date:	2021
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	1873-2968
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LONG-QT-SYNDROME; POLYMORPHIC VENTRICULAR-TACHYCARDIA; SODIUM-CHANNEL MUTATIONS; BRUGADA-SYNDROME; RYANODINE RECEPTOR; CALCIUM-RELEASE; CARDIOMYOCYTES; PHENOTYPE; MECHANISMS; MOUSE Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56308