Abstract
Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders of skeletal muscle causing weakness and disability. Utilizing single fibre contractility studies, we have previously shown that contractility is affected in muscle fibres from individuals with IIMs. For the current study, we hypothesized that a compensatory increase in shortening velocity occurs in muscle fibres from individuals with IIMs in an effort to maintain power output. We performed in vitro single fibre contractility studies to assess force–velocity relationships and maximum shortening velocity (Vmax) of muscle fibres from individuals with IIMs (25 type I and 58 type IIA) and healthy controls (66 type I and 27 type IIA) and calculated maximum power output (Wmax) for each fibre. We found significantly higher Vmax (mean ± SEM) of fibres from individuals with IIMs, for both type I (1.40 ± 0.31 fibre lengths/s, n = vs. 0.63 ± 0.13 fibre lengths/s; p = 0.0019) and type IIA fibres (2.00 ± 0.17 fibre lengths/s vs 0.77 ± 0.10 fibre lengths/s; p < 0.0001). Furthermore, Wmax (mean ± SEM) was maintained compared to fibres from healthy controls, again for both type I and type IIA fibres (4.10 ± 1.00 kN/m2·fibre lengths/s vs. 2.00 ± 0.16 kN/m2·fibre lengths/s; p = ns and 9.00 ± 0.64 kN/m2·fibre lengths/s vs. 6.00 ± 0.67 kN/m2·fibre lengths/s; p = ns respectively). In addition, type I muscle fibres from individuals with IIMs was able to develop maximum power output at lower relative force. The findings of this study suggest that compensatory responses to maintain power output, including increased maximum shortening velocity and improved efficiency, may occur in muscle of individuals with IIMs. The mechanism underlying this response is unclear, and different hypotheses are discussed.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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The experimental work was performed in the MyoLab of Professor Kohn, Division of Exercise Science and Sports Medicine, University of Cape Town. FH and TAK conceptualised and designed the study. FH performed the acquisition, analysis, and interpretation of the data, and drafted and revised the manuscript. TAK revised the manuscript. All authors approved the final version and takes full accountability for the accuracy of the manuscript content. All listed authors qualify for authorship.
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10974_2022_9638_MOESM1_ESM.tiff
Supplementary file1 (TIFF 3197 kb) Supplementary Fig. 1 Force–length traces of a type IIA muscle fibre from a healthy control. After attaining maximum force, the lever motor was controlled by the software to shorten the length of the fibre (right axis) to yield a predetermined percentage of absolute maximum force isotonically (force clamp, left axis). For this fibre, the series of force clamps corresponded to 80%, 55%, 30% and 10% of absolute maximum force, each lasting 150 ms. For each fibre, the shortening velocity was determined from the last 50 ms of each force clamp (length change), from which the slope was plotted against the force (% of maximum). After the last force clamp, the fibre was briefly shortened for 2 ms to 50% of its initial length, and rapidly re-stretched back to its original length. Three force clamp series followed, each series consisting of different percentages of maximum force. Once all the series were completed, the fibre was returned to the relaxing solution. P0 = maximum force
10974_2022_9638_MOESM2_ESM.tiff
Supplementary file2 (TIFF 3019 kb) Supplementary Fig. 2 Example of a sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of myosin heavy chain (MyHC) isoforms. MyHC isoforms were identified using a homogenate that contained all three human MyHC isoforms as control
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Henning, F., Kohn, T.A. Preservation of shortening velocity and power output in single muscle fibres from patients with idiopathic inflammatory myopathies. J Muscle Res Cell Motil 44, 1–10 (2023). https://doi.org/10.1007/s10974-022-09638-w
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DOI: https://doi.org/10.1007/s10974-022-09638-w