Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv
Abstract
:1. Introduction
2. Results
2.1. Isometric Force Production by Diaphragm Muscle
2.2. Effect of Tirasemtiv on Diaphragm Muscle Strip
2.3. Effect of Tirasemtiv on in Vivo Muscle Strength of Gastrocnemius Complex
3. Discussion
3.1. Contractile Performance in Neb cKO Diaphragm
3.2. Tirasemtiv Effect on Diaphragm
3.3. Contractility of Gastrocnemius Complex and Effects of Tirasemtiv
3.4. Conclusion
4. Material and Methods
4.1. Animal Model
4.2. Tirasemtiv
4.3. Ex-Vivo Diaphragm Muscle Mechanics
4.3.1. Muscle Experiments
4.3.2. Protocols
Force–Frequency Protocol
Force–Velocity Protocol
Analysis
4.4. In Vivo Strength Measurement of Gastrocnemius Muscle Complex
Protocols
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Ctrl | cKO | |||
---|---|---|---|---|
Vehicle | Tirasemtiv | Vehicle | Tirasemtiv | |
Diaphragm | n = 15 | n = 15 | n = 18 | n = 18 |
Specific force (mN/mm2) at 200 Hz | 200.0 ± 12.0 | 207.6 ± 11.7*** | 86.8 ± 7.0#### | 94.4 ± 6.9***,#### |
F50 frequency (Hz) | 33.4 ± 2.7 | 20.3 ± 2.3**** | 38.3 ± 2.4#### | 21.1 ± 2.1**** |
nH | 1.47 ± 0.1 | 1.05 ± 0.05 | 2.49 ± 0.13#### | 1.38 ± 0.09**** |
Velocity @ 0.1Fmax(Lo/sec) | 2.39 ± 0.1 | 4.05 ± 0.2**** | 1.75 ± 0.13#### | 2.47 ± 0.18**** |
Max Power((mN/mm2)x(Lo/s)) | 65.0 ± 5.4 | 115.7 ± 7.9**** | 24.6 ± 3.7#### | 37.5 ± 5.3**** |
Gastrocnemius complex | n = 9 | n = 9 | n = 11 | n = 11 |
Specific force (mN/mg) at 200 Hz | 2.50 ± 0.07 | 2.39 ± 0.08 | 0.81 ± 0.04#### | 0.85 ± 0.03#### |
F50 frequency (Hz) | 57.9 ± 1.3 | 39.1 ± 2.7**** | 37.2 ± 1.4#### | 27.3 ± 1.5**# |
nH | 4.9 ± 0.5 | 2.7 ± 0.5** | 3.6 ± 0.5# | 2.5 ± 0.5* |
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Lee, E.-J.; Kolb, J.; Hwee, D.T.; Malik, F.I.; Granzier, H.L. Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv. Int. J. Mol. Sci. 2019, 20, 5008. https://doi.org/10.3390/ijms20205008
Lee E-J, Kolb J, Hwee DT, Malik FI, Granzier HL. Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv. International Journal of Molecular Sciences. 2019; 20(20):5008. https://doi.org/10.3390/ijms20205008
Chicago/Turabian StyleLee, Eun-Jeong, Justin Kolb, Darren T. Hwee, Fady I. Malik, and Henk L. Granzier. 2019. "Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv" International Journal of Molecular Sciences 20, no. 20: 5008. https://doi.org/10.3390/ijms20205008