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Non-cell autonomous cues for enhanced functionality of human embryonic stem cell-derived cardiomyocytes via maturation of sarcolemmal and mitochondrial K ATP channels.
- Source :
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Scientific reports [Sci Rep] 2016 Sep 28; Vol. 6, pp. 34154. Date of Electronic Publication: 2016 Sep 28. - Publication Year :
- 2016
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Abstract
- Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (K <subscript>ATP</subscript> ) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcK <subscript>ATP</subscript> and mitoK <subscript>ATP</subscript> in hESC-VCM. We showed that SarcI <subscript>K, ATP</subscript> in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known opener P1075 with a current density that was ~8-fold smaller than adult; These effects were reversible upon washout or the addition of GLI or HMR1098. Interestingly, sarcI <subscript>K, ATP</subscript> displayed a ~3-fold increase after treatment with hypoxia (5% O <subscript>2</subscript> ). MitoI <subscript>K, ATP</subscript> was absent in hESC-VCMs. However, the thyroid hormone T3 up-regulated mitoI <subscript>K, ATP,</subscript> conferring diazoxide protective effect on T3-treated hESC-VCMs. When assessed using a multi-cellular engineered 3D ventricular cardiac micro-tissue (hvCMT) system, T3 substantially enhanced the developed tension by 3-folds. Diazoxide also attenuated the decrease in contractility induced by simulated ischemia (1% O <subscript>2</subscript> ). We conclude that hypoxia and T3 enhance the functionality of hESC-VCMs and their engineered tissues by selectively acting on sarc and mitoI <subscript>K, ATP</subscript> .
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27677332
- Full Text :
- https://doi.org/10.1038/srep34154