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. 2020 Jan 27;141(10):828–842. doi: 10.1161/CIRCULATIONAHA.119.042339

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© 2020 The Authors.

Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

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Figure 3. — Pathogenic hypertrophic cardiomyopathy myosin variants in mouse cardiomyocytes and iPSC-CMs exhibit hypercontractility and abnormal relaxation that is normalized by interacting heads motif restabilization with MYK-461. A, Mouse cardiomyocytes (×40 image) shows precise striations attributable to a well-organized sarcomere. B, Typical contractile waveform obtained by tracking strings of mouse cardiomyocyte sarcomeres during 1 Hz pacing. C and D, Sarcomere shortening (C) and relaxation durations (D) in WT, Myh6^R403Q/+, Myh6^V606M/+, and Myh6^R719W/+ mouse cardiomyocytes taken from 3 hearts per genotype. E and F, Dose-dependent effects of acute MYK-461 application on sarcomere contractility (E, percent shortening) and relaxation (F) in paced mouse WT, Myh6^R403Q/+, Myh6^V606M/+, and Myh6^R719W/+ cardiomyocytes from 3 hearts per genotype. G, Image of titin-green fluorescent protein–tagged iPSC-CM imaged at 100×, showing z-discs labeled by green fluorescence. H, Contractile waveform of a single sarcomere defined by a z-disc pair during 1 Hz pacing. I and J, Sarcomere shortening (I) and relaxation durations (J) in paced isogenic WT, MYH7^R403Q/+, MYH7^V606M/+, and MYH7^R719W/+ iPSC-CMs from 3 separate differentiations. K and L, Dose-dependent effect of acute MYK-461 application on sarcomere contractility (K) and relaxation durations (L) in paced isogenic WT, MYH7^R403Q/+, MYH7^V606M/+, and MYH7^R719W/+ iPSC-CMs from 3 separate differentiations. Significant differences to WT were assessed by 2-way ANOVA with post hoc Bonferroni correction from multiple comparisons, significances of P<0.05 indicated by *. All data are displayed as mean±SEM. iPSC-CMs indicates isogenic cardiomyocytes derived from induced pluripotent stem cells; and WT, wild type cardiomyocytes.