hiPSC-Derived Cardiomyocyte Model of LQT2 Syndrome Derived from Asymptomatic and Symptomatic Mutation Carriers Reproduces Clinical Differences in Aggregates but Not in Single Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
2.2. Genetic Screening
2.3. hiPSC Generation, Culture and Characterization
2.4. Cardiomyocyte Differentiation
2.5. Allelic Imbalance
2.6. HERG Channel Expression in HEK-293 Expression System
2.7. Ca2+ Imaging
2.8. Voltage Clamp
2.9. Micro Electrode Array (MEA) Electrophysiology
2.10. Mathematical Modeling and Computer Simulations of CM Function
2.11. Statistics
3. Results
4. Discussion
4.1. What Is the Mechanism for Reduced HERG Channel Function?
4.2. What Is Causing Arrhythmogenic Events in LQT2?
4.3. Limitations of the Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Shah, D.; Prajapati, C.; Penttinen, K.; Cherian, R.M.; Koivumäki, J.T.; Alexanova, A.; Hyttinen, J.; Aalto-Setälä, K. hiPSC-Derived Cardiomyocyte Model of LQT2 Syndrome Derived from Asymptomatic and Symptomatic Mutation Carriers Reproduces Clinical Differences in Aggregates but Not in Single Cells. Cells 2020, 9, 1153. https://doi.org/10.3390/cells9051153
Shah D, Prajapati C, Penttinen K, Cherian RM, Koivumäki JT, Alexanova A, Hyttinen J, Aalto-Setälä K. hiPSC-Derived Cardiomyocyte Model of LQT2 Syndrome Derived from Asymptomatic and Symptomatic Mutation Carriers Reproduces Clinical Differences in Aggregates but Not in Single Cells. Cells. 2020; 9(5):1153. https://doi.org/10.3390/cells9051153
Chicago/Turabian StyleShah, Disheet, Chandra Prajapati, Kirsi Penttinen, Reeja Maria Cherian, Jussi T. Koivumäki, Anna Alexanova, Jari Hyttinen, and Katriina Aalto-Setälä. 2020. "hiPSC-Derived Cardiomyocyte Model of LQT2 Syndrome Derived from Asymptomatic and Symptomatic Mutation Carriers Reproduces Clinical Differences in Aggregates but Not in Single Cells" Cells 9, no. 5: 1153. https://doi.org/10.3390/cells9051153