Universität zu Köln

Semmler, Judith, Lehmann, Martin, Pfannkuche, Kurt, Reppel, Michael, Hescheler, Juergen and Nguemo, Filomain (2014). Functional Expression and Regulation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (HCN) in Mouse iPS Cell-derived Cardiomyocytes after UTF1-Neo Selection. Cell. Physiol. Biochem., 34 (4). S. 1199 - 1216. BASEL: KARGER. ISSN 1421-9778

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Abstract

Background/Aims: In vitro reprogramming of somatic cells holds great potential to serve as an autologous source of cells for tissue repair. However, major difficulties in achieving this potential include obtaining homogeneous and stable cells for transplantation. High electrical activity of cells such as cardiomyocytes (CMs) is crucial for both, safety and efficiency of cell replacement therapy. Moreover, the function of the cardiac pacemaker is controlled by the activities of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here we have examined changes in HCN gene expression and function during cardiomyogenesis. Methods: We differentiated murine iPS cells selected by an undifferentiated transcription factor 1 (UTF1) -promoter-driven G418 resistance to CMs in vitro and characterized them by RT-PCR, immunocytochemistry, and electrophysiology. Results: As key cardiac markers alpha-actinin and cardiac troponin T could be identified in derived CMs. Immunocytochemical staining of CMs showed the presence of all HCN subunits (HCN1-4). Electrophysiology experiments revealed developmental changes of action potentials and I-f currents as well as functional hormonal regulation and sensitivity to If channel blockers. Conclusion: We conclude that iPS cells derived from UTF-selection give rise to functional CMs in vitro, with established hormonal regulation pathways and functionally expressed If current in a development-dependent manner; and have all phenotypes with the pacemaker as predominant subtype. This might be of great importance for transplantation purposes. Copyright (C) 2014 S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Semmler, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfannkuche, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED Reppel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-449436
DOI:	10.1159/000366332
Journal or Publication Title:	Cell. Physiol. Biochem.
Volume:	34
Number:	4
Page Range:	S. 1199 - 1216
Date:	2014
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1421-9778
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EMBRYONIC STEM-CELLS; IN-VITRO; PACEMAKER ACTIVITY; CARDIAC MYOCYTES; SINOATRIAL NODE; VENTRICULAR MYOCYTES; CATION CHANNELS; FUNNY CURRENT; CURRENT I(F); F-CHANNELS Multiple languages Cell Biology; Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44943