Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells
Abstract
:1. Introduction
2. Results
2.1. BeKm-1 Is a High-Affinity Blocker of hERG Channel
2.2. BeKm-1 Produces Characteristic Modifications of the Action Potential (AP) in hiPS-CMs
2.3. Proarrhythmic Effects of BeKm-1 in Dynamic Clamp Conditions
2.4. BeKm-1 Alters Excitatory Field Potentials of hiPS-CMs
2.5. BeKm-1 Indirectly Alters the Ca2+ Dynamics and Contraction Properties of hiPS-CMs
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes and HEK-293 Cell Culture
4.3. Manual and Automated Patch-Clamp Experiments
4.4. Beating Assessment and Electrical Field Potential Measurements of hiPS-CMs
4.5. Calcium Transient Recordings
4.6. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AP | Action potential |
APD | Action potential duration |
EAD | Early afterdepolarization |
ECG | Electrocardiogram |
ECC | Excitation-contraction coupling |
EFP | Electric field potential |
EGTA | Ethylene glycol tetraacetic acid |
GPCRs | G protein-coupled receptors |
HEK293 | Human embryonic kidney 293 cells |
HEPES | 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid |
hERG | human Ether-à-go-go-Related Gene |
hiPS-CMs | Human induced pluripotent stem cell-derived cardiomyocytes |
KCNH2 | Gene encoding hERG channel |
LQTS | Long QT syndrome |
MDP | Maximum diastolic potential |
NCX | Sodium/calcium exchangers |
PW | pulse widths |
RMP | Resting membrane potential |
SAN | Sinoatrial node |
SERCA | Sarco/endoplasmic reticulum Ca2+ ATPase |
TdP | Torsades de pointes |
VGCC | Voltage-gated calcium channels |
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De Waard, S.; Montnach, J.; Ribeiro, B.; Nicolas, S.; Forest, V.; Charpentier, F.; Mangoni, M.E.; Gaborit, N.; Ronjat, M.; Loussouarn, G.; et al. Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells. Int. J. Mol. Sci. 2020, 21, 7167. https://doi.org/10.3390/ijms21197167
De Waard S, Montnach J, Ribeiro B, Nicolas S, Forest V, Charpentier F, Mangoni ME, Gaborit N, Ronjat M, Loussouarn G, et al. Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells. International Journal of Molecular Sciences. 2020; 21(19):7167. https://doi.org/10.3390/ijms21197167
Chicago/Turabian StyleDe Waard, Stephan, Jérôme Montnach, Barbara Ribeiro, Sébastien Nicolas, Virginie Forest, Flavien Charpentier, Matteo Elia Mangoni, Nathalie Gaborit, Michel Ronjat, Gildas Loussouarn, and et al. 2020. "Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells" International Journal of Molecular Sciences 21, no. 19: 7167. https://doi.org/10.3390/ijms21197167