Momb Brent A, Chipkin Stuart R, Kent Jane A, Miller Mark S
bioRxiv. 2025 Aug 27:2025.08.27.670366. doi: 10.1101/2025.08.27.670366.
As human skeletal muscle cellular and molecular contractile properties are temperature-sensitive, the ability to perform experiments at body temperature (∼37°C) may lead to a better understanding of their responses and potentially their effects upon whole-muscle and whole-body performance. We quantified molecular (myosin-actin cross-bridge mechanics and kinetics) and cellular (specific tension; force divided by cross-sectional area) function in slow-contracting myosin heavy chain (MHC) I and fast-contracting MHC IIA fibers from older adults (n=13, 8 female) at 37°C and compared these to results at 25°C. MHC I fibers were more temperature-sensitive than MHC IIA fibers, showing greater increases in cross-bridge kinetics (MHC I: 4.9-8.7x; IIA: 4x) and number or stiffness of strongly-bound cross-bridges (MHC I: 86%; IIA: 34%), leading to increased specific tension in MHC I (19%), with no change in MHC IIA fibers. The expected relationship between fiber force and size (cross-sectional area, CSA) was stronger at 37°C in both fiber types, explaining 80-82% of the variance compared to 51-52% at 25°C. Specific tension was unchanged with size at 37°C in both fiber types, showing that force increases proportionally with CSA, which may be due to the increased number or stiffness of strongly-bound cross-bridges at this temperature. At 25°C, specific tension decreased with size in agreement with previous experiments. Overall, MHC I and IIA fibers at body temperature (37°C) became more analogous, including similar specific tension and closer cross-bridge kinetics, and force production was more strongly correlated with fiber size compared to a non-physiological temperature.
Although skeletal muscle function is highly sensitive to temperature, human single fiber studies have only been conducted at ≤30°C.Small-amplitude sinusoidal perturbations were utilized to elucidate mechanisms of single fiber force production at human physiological temperature (37°C).We found that functional differences in slow-contracting myosin heavy chain (MHC I) and fast-contracting MHC IIA fibers observed at 25°C were less apparent at 37°C, as force, crossbridge kinetics, and strongly-bound crossbridges increased more in MHC I fibers than MHC IIA fibers at 37 vs. 25°C. These results indicate that, given the different sensitivity of each fiber type to changes in temperature, functional assessments of muscle should be conducted at 37°C to better translate to conditions.
由于人类骨骼肌的细胞和分子收缩特性对温度敏感，在体温（约37°C）下进行实验的能力可能有助于更好地理解其反应以及对全肌肉和全身性能的潜在影响。我们在37°C下对老年人（n = 13，8名女性）的慢收缩肌球蛋白重链（MHC）I型和快收缩MHC IIA型纤维的分子（肌球蛋白 - 肌动蛋白横桥力学和动力学）和细胞（比张力；力除以横截面积）功能进行了量化，并将这些结果与25°C时的结果进行比较。MHC I型纤维比MHC IIA型纤维对温度更敏感，横桥动力学增加幅度更大（MHC I：4.9 - 8.7倍；IIA：4倍），强结合横桥的数量或刚度增加更多（MHC I：86%；IIA：34%），导致MHC I型纤维比张力增加（19%），而MHC IIA型纤维无变化。两种纤维类型在37°C时纤维力与大小（横截面积，CSA）之间的预期关系更强，解释了80 - 82%的方差，而在25°C时为51 - 52%。两种纤维类型在37°C时比张力不随大小变化，表明力与CSA成比例增加，这可能是由于在此温度下强结合横桥的数量或刚度增加。在25°C时，比张力随大小降低，与先前实验一致。总体而言，体温（37°C）下的MHC I型和IIA型纤维变得更相似，包括类似的比张力和更接近的横桥动力学，并且与非生理温度相比，力产生与纤维大小的相关性更强。
尽管骨骼肌功能对温度高度敏感，但人体单纤维研究仅在≤30°C下进行。利用小幅度正弦扰动来阐明人体生理温度（37°C）下单纤维力产生的机制。我们发现，在25°C时观察到的慢收缩肌球蛋白重链（MHC I）和快收缩MHC IIA型纤维的功能差异在37°C时不太明显，因为在37°C与25°C相比，MHC I型纤维中的力、横桥动力学和强结合横桥增加得更多。这些结果表明，鉴于每种纤维类型对温度变化的敏感性不同，肌肉功能评估应在37°C下进行，以便更好地转化为实际情况。
