bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.06.10.598225

Residual force enhancement decreases when scaling from the single muscle fibre to joint level in humans

Abstract

Residual force enhancement (rFE), defined as increased isometric force following active lengthening compared to a fixed-end isometric contraction at the same muscle length and level of activation, is present across all scales of muscle. While rFE is always present at the cellular level, often rFE non-responders are observed during joint-level voluntary contractions. We compared rFE between the joint level and single fibre level (vastus lateralis biopsies) in 16 young males. In-vivo voluntary knee-extensor rFE was measured by comparing steady-state isometric torque between a stretch-hold (maximal activation at 150{degrees}, stretch to 70{degrees}, hold) and a fixed-end isometric contraction, with ultrasonographic recording of vastus lateralis fascicle length (FL). Fixed-end contractions were performed at 67.5{degrees}, 70{degrees}, 72.5{degrees}, and 75{degrees}; the joint angle that most closely matched FL of the stretch-hold contractions isometric steady-state was used to calculate rFE. The starting and ending FLs of the stretch-hold contraction were expressed as % optimal FL, determined via torque-angle relationship. In single fibre experiments, the starting and ending fibre lengths were matched relative to optimal length determined from in-vivo testing, yielding an average sarcomere excursion of [~]2.2-3.4{micro}m. There was a greater magnitude of rFE at the single fibre ([~]20%) than joint level ([~]5%) (P=0.004), with non-responders only observed at the joint level. By comparing rFE across scales within the same participants, we show the development of the rFE non-responder phenomenon is upstream of rFEs cellular mechanisms, with rFE only lost rather than gained when scaling from single fibres to the joint level.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hinks, A., Jacob, K. B. E., Patterson, M. A., Dalton, B., Power, G. A.. 2024-06-11. Residual force enhancement decreases when scaling from the single muscle fibre to joint level in humans. https://doi.org/10.1101/2024.06.10.598225

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Hypothalamic Farnesoid X Receptor deficiency alters energy balance by modulating hepatic glucose production and adipose tissue metabolism through central insulin signaling.

Objectives: The bile acid nuclear receptor Farnesoid X Receptor (FXR, NR1H4) is a major regulator of metabolism and energy homeostasis in peripheral organs. It modulates bile acid, glucose, and lipid metabolism, as well as fat mass and body weight. However, FXR is also expressed in the brain, particularly in the hypothalamus, a key center for the regulation of energy homeostasis. Although one study has demonstrated a role for brain FXR activation in energy balance, its specific hypothalamic role is still unknown. Here, we examined the role of FXR in the mediobasal hypothalamus in the regulation of energy balance. Methods: We used a genetic approach combined with metabolic phenotyping to determine the effect of FXR invalidation in the mediobasal hypothalamus on metabolic parameters involved in the central regulation of energy homeostasis. Results: Our results demonstrate that hypothalamic FXR deficiency induces a positive energy balance, resulting in a reduction in energy expenditure due to alterations in glucose metabolism accompanied by structural changes in white adipose tissues. Conclusion: This study uncovers a previously unrecognized role for hypothalamic FXR in the central homeostatic control of energy balance, providing new insights into its contribution to peripheral glucose metabolism and adipose tissue structural remodeling.

physiology↗

Rad and Phospholamban are Key Drivers of the Ventricular Adrenergic Response and Stress-Induced Arrhythmia

The adrenergic response is a fundamental mechanism that regulates heart rate (chronotropy), cardiac contractility (inotropy) and relaxation (lusitropy). Adrenergic stress is also a recognized trigger of arrhythmia in disease. Yet, our understanding of the underlying molecular basis remains incomplete. Protein kinase A (PKA) and the calcium/calmodulin-dependent kinase II (CaMKII) phosphorylate multiple targets proposed to participate in the adrenergic response, including the GTP-binding protein Rad, phospholamban (PLB) and ryanodine receptor 2 (RyR2). Here we demonstrate that phosphorylation of both Rad and PLB is necessary for inotropy and lusitropy. We show that changes in cardiac contractility and relaxation are primarily dependent on intracellular calcium handling. Finally, we report that Rad and PLB control stress-induced arrhythmogenesis, despite the phosphorylation of other pro-arrhythmic targets. We have identified the essential molecular components of the adrenergic response, resolving a long-standing debate in cardiac excitation-contraction coupling and refining current models of sympathetic regulation in health and disease.

physiology↗

Light-cycle time-restricted feeding remodels a hidden layer of the cardiac transcriptome through sex-specific transcript switching

Light-cycle time-restricted feeding disrupts daily cardiovascular and thermoregulatory rhythms, but the molecular effects of light-cycle time-restricted feeding on the heart have been measured only at the level of total gene expression. We used Oxford Nanopore long-read RNA sequencing to resolve the full-length ventricular transcriptome from male and female mice under ad libitum feeding or light-cycle time-restricted feeding across the 24-hour cycle. Greater than 20% of cardiac transcripts represent unannotated variants of known genes absent from the current GENCODE reference annotation. Light-cycle time-restricted feeding reorganizes transcript usage across hundreds of genes, including genes encoding splicing regulators, largely without changing total gene expression. The genes affected are sex-specific, with fewer than 2% of changes shared at the gene, transcript, and transcript-usage levels. We show that transcript-level regulation is a previously underrecognized component of the cardiac response to altered feeding behavior, undetected by conventional short-read approaches.

physiology↗