Universität zu Köln

Fatima, Azra, Dittmann, Sven, Xu, Guoxing, Gupta, Manoj K., Linke, Matthias, Zechner, Ulrich, Nguemo, Filomain, Milting, Hendrik, Farr, Martin, Hescheler, Juergen and Saric, Tomo ORCID: 0000-0001-8344-1095 (2013). The Disease-Specific Phenotype in Cardiomyocytes Derived from Induced Pluripotent Stem Cells of Two Long QT Syndrome Type 3 Patients. PLoS One, 8 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Long QT syndromes (LQTS) are heritable diseases characterized by prolongation of the QT interval on an electrocardiogram, which often leads to syncope and sudden cardiac death. Here we report the generation of induced pluripotent stems (iPS) cells from two patients with LQTS type 3 carrying a different point mutation in a sodium channel Na(v)1.5 (p.V240M and p.R535Q) and functional characterization of cardiomyocytes (CM) derived from them. The iPS cells exhibited all characteristic properties of pluripotent stem cells, maintained the disease-specific mutation and readily differentiated to CM. The duration of action potentials at 50% and 90% repolarization was longer in LQTS-3 CM as compared to control CM but this difference did not reach statistical significance due to high variations among cells. Sodium current recordings demonstrated longer time to peak and longer time to 90% of inactivation of the Na+ channel in the LQTS-3 CM. This hints at a defective Na+ channel caused by deficiency in open-state inactivation of the Na+ channel that is characteristic of LQTS-3. These analyses suggest that the effect of channel mutation in the diseased CM is demonstrated in vitro and that the iPS cell-derived CM can serve as a model system for studying the pathophysiology of LQTS-3, toxicity testing and design of novel therapeutics. However, further improvements in the model are still required to reduce cell-to-cell and cell line-to-cell line variability.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fatima, Azra UNSPECIFIED UNSPECIFIED UNSPECIFIED Dittmann, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Xu, Guoxing UNSPECIFIED UNSPECIFIED UNSPECIFIED Gupta, Manoj K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Linke, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Zechner, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED Milting, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Farr, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED orcid.org/0000-0001-8344-1095 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-470165
DOI:	10.1371/journal.pone.0083005
Journal or Publication Title:	PLoS One
Volume:	8
Number:	12
Date:	2013
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BRUGADA-SYNDROME; SCN5A MUTATIONS; VENTRICULAR-TACHYCARDIA; SPLICE VARIANT; IN-VITRO; PREVALENCE; ARRHYTHMIA; EXPRESSION; SPECTRUM; MODEL Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47016