Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle
Abstract
:1. Introduction
2. Results
2.1. OM Induces a Rapid and Fully Reversible Modulation of Force Generation in Human Atrial and Ventricular Myofibrils
2.2. HV Myofibrils: OM Increases Tension and Decreases the Kinetics of Force Generation and Relaxation Simultaneously Perturbing the Regulation State of Ventricular β-Slow MyHC-7 Sarcomeres
2.3. HA Myofibrils: OM Increases Submaximal Tension and Decreases the Kinetics of Force Generation and Relaxation with Little Effect on the Regulatory State of Atrial α-Fast MyHC-6 Sarcomeres
2.4. OM Reduces the Inhibition of Force by Pi in the Low [Pi] Range
2.5. Effect of OM on the Resting Tension and ATPase of Skinned Strips of Human Ventricular Muscle
3. Discussion
4. Methods
4.1. Preparation of Myofibrils from Human Cardiac Sample
4.2. Electrophoretic Assays
4.3. Myofibril Experiments
4.4. Cardiac Strip Experiments
4.5. Solutions for Mechanical Experiments
4.6. Data Acquisition and Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Tension Generation | Relaxation | ||||
---|---|---|---|---|---|
Slow Phase | Fast Phase | ||||
P0 | kACT | kTR | Duration | slow kREL | fast kREL |
mN mm−2 | s−1 | s−1 | ms | s−1 | s−1 |
Human ventricle | |||||
82 ± 5 (55) | 0.60 ± 0.04 (23) | 0.44 ± 0.01 (54) | 173 ± 10 (23) | 0.42 ± 0.05 (22) | 4.95 ± 0.34 (23) |
Human atrium | |||||
82 ± 6 (49) | 3.51 ± 0.41 (14) | 2.96 ± 0.16 (44) | 108 ± 6 (14) | 0.58 ± 0.03 (14) | 14.3 ± 0.82 (14) |
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Scellini, B.; Piroddi, N.; Dente, M.; Pioner, J.M.; Ferrantini, C.; Poggesi, C.; Tesi, C. Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle. Int. J. Mol. Sci. 2024, 25, 9784. https://doi.org/10.3390/ijms25189784
Scellini B, Piroddi N, Dente M, Pioner JM, Ferrantini C, Poggesi C, Tesi C. Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle. International Journal of Molecular Sciences. 2024; 25(18):9784. https://doi.org/10.3390/ijms25189784
Chicago/Turabian StyleScellini, Beatrice, Nicoletta Piroddi, Marica Dente, J. Manuel Pioner, Cecilia Ferrantini, Corrado Poggesi, and Chiara Tesi. 2024. "Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle" International Journal of Molecular Sciences 25, no. 18: 9784. https://doi.org/10.3390/ijms25189784