Myofilament Calcium-Buffering Dependent Action Potential Triangulation in Human-Induced Pluripotent Stem Cell Model of Hypertrophic Cardiomyopathy

[...]the unedited line was the isogenic control line. Pre-treatment with the Ca desensitizer blebbistatin (3 μmol/l) or excess cytosolic buffering (by adding 14 mmol/l ethylene glycol tetraacetic acid to intracellular solutions) prevented AP triangulation (Figure 1B). Taken together, our results ind...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2017-11, Vol.70 (20), p.2600-2602
Main Authors: Wang, Lili, Kryshtal, Dmytro O., Kim, Kyungsoo, Parikh, Shan, Cadar, Adrian Gabriel, Bersell, Kevin Richard, He, Huan, Pinto, Jose R., Knollmann, Bjorn C.
Format: Article
Language:English
Subjects:
Action potential
Action Potentials - physiology
Calcium
Calcium buffering
Calcium Signaling - physiology
Cardiology
Cardiomyocytes
Cardiomyopathy
Cardiomyopathy, Hypertrophic - physiopathology
Cell Culture Techniques
Cell Line
Human influences
Humans
Induced Pluripotent Stem Cells - physiology
Mutation
Myofibrils - physiology
Pluripotency
Population
Stem cells
Triangulation
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Summary:[...]the unedited line was the isogenic control line. Pre-treatment with the Ca desensitizer blebbistatin (3 μmol/l) or excess cytosolic buffering (by adding 14 mmol/l ethylene glycol tetraacetic acid to intracellular solutions) prevented AP triangulation (Figure 1B). Taken together, our results indicate that myofilament-dependent increase in cytosolic Ca buffering shortens early repolarization via a Ca-dependent, NCX-mediated mechanism, resulting in AP triangulation and AP instability, both of which are well-established predictors of increased arrhythmia risk (5).
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2017.09.033