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Do skeletal muscle motor units and microvascular units align to help match blood flow to metabolic demand?
Murrant, CL, Fletcher, NM, Fitzpatrick, EJH, Gee, KS
European journal of applied physiology. 2021;(5):1241-1254
Abstract
PURPOSE We explore the motor unit recruitment and control of perfusion of microvascular units in skeletal muscle to determine whether they coordinate to match blood flow to metabolic demand. METHODS The PubMed database was searched for historical, current and relevant literature. RESULTS A microvascular, or capillary unit consists of 2-20 individual capillaries. Individual capillaries within a capillary unit cannot increase perfusion independently of other capillaries within the unit. Capillary units perfuse a short segment of approx. 12 muscle fibres located beside each other. Motor units consist of muscle fibres that can be dispersed widely within the muscle volume. During a contraction, where not all motor units are recruited, muscle fibre contraction will result in increased perfusion of associated capillaries as well as all capillaries within that capillary unit. Perfusion of the entire capillary unit will result in an increased blood flow delivery to muscle fibres associated with active motor unit plus approximately 11 other inactive muscle fibres within the same region. This will result in an overperfusion of the muscle resulting in blood flow in excess of the muscle fibre needs. CONCLUSIONS Given the architecture of the capillary units and the dispersed nature of muscle fibres within a motor unit, during submaximal contractions, where not all motor units are recruited, there will be a greater perfusion to the muscle than that predicted by the number of active muscle fibres. Such overperfusion brings into question if blood flow and metabolic demand are as tightly matched as previously assumed.
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Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions.
Olivé, M, Engvall, M, Ravenscroft, G, Cabrera-Serrano, M, Jiao, H, Bortolotti, CA, Pignataro, M, Lambrughi, M, Jiang, H, Forrest, ARR, et al
Nature communications. 2019;(1):1396
Abstract
Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
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Relationship of Physical Function to Single Muscle Fiber Contractility in Older Adults: Effects of Resistance Training With and Without Caloric Restriction.
Wang, ZM, Leng, X, Messi, ML, Choi, SJ, Marsh, AP, Nicklas, B, Delbono, O
The journals of gerontology. Series A, Biological sciences and medical sciences. 2019;(3):412-419
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Abstract
BACKGROUND Previous studies support beneficial effects of both resistance exercise training (RT) and caloric restriction (CR) on skeletal muscle strength and physical performance. The goal of this study was to determine the effects of adding CR to RT on single-muscle fiber contractility responses to RT in older overweight and obese adults. METHODS We analyzed contractile properties in 1,253 single myofiber from muscle biopsies of the vastus lateralis, as well as physical performance and thigh muscle volume, in 31 older (65-80 years), overweight or obese (body mass index = 27-35 kg/m2) men (n = 19) and women (n = 12) who were randomly assigned to a standardized, progressive RT intervention with CR (RT+CR; n = 15) or without CR (RT; n = 16) for 5 months. RESULTS Both interventions evoked an increase in force normalized to cross-sectional area (CSA), in type-I and type-II fibers and knee extensor quality. However, these improvements were not different between intervention groups. In the RT group, changes in total thigh fat volume inversely correlated with changes in type-II fiber force (r = -.691; p = .019). Within the RT+CR group, changes in gait speed correlated positively with changes in type-I fiber CSA (r = .561; p = .030). In addition, increases in type-I normalized fiber force were related to decreases in thigh intermuscular fat volume (r = -0.539; p = .038). CONCLUSION Single muscle fiber force and knee extensor quality improve with RT and RT+CR; however, CR does not enhance improvements in single muscle fiber contractility or whole muscle in response to RT in older overweight and obese men and women.
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Fiber typing human skeletal muscle with fluorescent immunohistochemistry.
Murach, KA, Dungan, CM, Kosmac, K, Voigt, TB, Tourville, TW, Miller, MS, Bamman, MM, Peterson, CA, Toth, MJ
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(6):1632-1639
Abstract
Skeletal muscle myosin heavy chain (MyHC) fiber type composition is a critical determinant of overall muscle function and health. Various approaches interrogate fiber type at the single cell, but the two most commonly utilized are single-muscle fiber sodium dodecyl sulfate-polyacrylamide gel electrophoresis (smfSDS-PAGE) and fluorescent immunohistochemistry (IHC). Although smfSDS-PAGE is generally considered the "gold standard," IHC is more commonly used because of its time-effectiveness and relative ease. Unfortunately, there is lingering inconsistency on how best to accurately and quickly determine fiber type via IHC and an overall misunderstanding regarding pure fiber type proportions, specifically the abundance of fibers exclusively expressing highly glycolytic MyHC IIX in humans. We therefore 1) present information and data showing the low abundance of pure MyHC IIX muscle fibers in healthy human skeletal muscle and 2) leverage this information to provide straightforward protocols that are informed by human biology and employ inexpensive, easily attainable antibodies for the accurate determination of fiber type.
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Extraocular muscles involved in convergence are innervated by an additional set of palisade endings that may differ in their excitability: A human study.
Lienbacher, K, Sänger, K, Strassburger, S, Ehrt, O, Rudolph, G, Barnerssoi, M, Horn, AKE
Progress in brain research. 2019;:127-137
Abstract
Palisade endings are located at the myotendinous junction of extraocular muscles in most mammals. Irrespective of their unclarified function as motor or sensory nerve endings, a specialized role in convergence is proposed, based on their high number in the medial rectus muscle (MR). Further support comes from a study in monkey demonstrating that only the MR and inferior rectus muscle (IR) contain an additional population of palisade endings that express the calcium-binding protein calretinin (CR) in addition to choline acetyltransferase (ChAT). Here we studied, whether CR-positive palisade endings are present in human as well and confined to extraocular muscles most active during convergence. The systematic analysis of all eye muscles of 17 human specimen revealed that only the MR and IR contain an additional population of CR-positive palisade endings and multiple en-grappe endings, which target non-twitch muscle fibers along their whole length. Approximately 80% of all palisade endings in the MR expressed CR. Furthermore, the intrafusal muscle fibers of some muscle spindles in the MR were innervated by CR-positive annulospiral nerve endings that transmit the signals of muscle length changes to the brain. All extraocular muscles contained few thin CR-positive, but ChAT-negative nerve fibers, possibly representing free sensory or autonomic endings arising from the trigeminal ganglion. As in monkey, in the medial periphery of the human oculomotor nucleus ChAT-positive neurons were found to co-express CR. Therefore these neurons most likely represent the cell bodies of CR-positive palisade endings in the MR. Unlike in monkey, these neurons do not lie within a compact cell group, but are more scattered. In conclusion, the MR and IR in human contain two histochemically different populations of palisade and multiple endings that may contribute to ocular alignment and convergence in a different way.
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High-intensity interval, but not endurance, training induces muscle fiber type-specific subsarcolemmal lipid droplet size reduction in type 2 diabetic patients.
Koh, HE, Ørtenblad, N, Winding, KM, Hellsten, Y, Mortensen, SP, Nielsen, J
American journal of physiology. Endocrinology and metabolism. 2018;(5):E872-E884
Abstract
This study compared the effects of moderate-intensity endurance training and high-intensity interval training on fiber type-specific subcellular volumetric content and morphology of lipid droplets and mitochondria in skeletal muscles of type 2 diabetic patients. Sixteen sedentary type 2 diabetic patients (57 ± 7 yr old) were randomized to complete 11 wk of either 40-min cycling at 50% peak workload (Endurance, n = 8) or 10 1-min cycling intervals at 95% peak workload separated by 1 min of recovery (High-Intensity Interval, n = 8), three times per week. Assessments for cardiorespiratory fitness, body composition, glycemic control, together with muscle biopsies were performed before and after the intervention. Morphometric analyses of lipid droplets and mitochondria were conducted in the subcellular fractions of biopsied muscle fibers using quantitative electron microscopy. The training intervention increased cardiorespiratory fitness, lowered fat mass, and improved nonfasting glycemic control ( P < 0.05), with no difference between training modalities. In the subsarcolemmal space, training decreased lipid droplet volume ( P = 0.003), and high-intensity interval, but not endurance, training reduced the size of lipid droplets, specifically in type 2 fibers ( P < 0.001). No training-induced change in intermyofibrillar lipid droplets was observed in both fiber types. Subsarcolemmal mitochondrial volume was increased by high-intensity interval ( P = 0.02), but not endurance, training ( P = 0.79). Along with improvement in glycemic control, low-volume high-intensity interval training is an alternative time-saving training modality that affects subcellular morphology and volumetric content of lipid droplets in skeletal muscle of type 2 diabetic patients.
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Muscle Fiber Hypertrophy and Myonuclei Addition: A Systematic Review and Meta-analysis.
Conceição, MS, Vechin, FC, Lixandrão, M, Damas, F, Libardi, CA, Tricoli, V, Roschel, H, Camera, D, Ugrinowitsch, C
Medicine and science in sports and exercise. 2018;(7):1385-1393
Abstract
INTRODUCTION The myonuclear domain theory postulates that myonuclei are added to muscle fibers when increases in fiber cross-sectional area (i.e., hypertrophy) are ≥26%. However, recent studies have reported increased myonuclear content with lower levels (e.g., 12%) of muscle fiber hypertrophy. PURPOSE This study aimed to determine whether a muscle fiber hypertrophy "threshold" is required to drive the addition of new myonuclei to existing muscle fibers. METHODS Studies of resistance training endurance training with or without nutrient (i.e., protein) supplementation and steroid administration with measures of muscle fiber hypertrophy and myonuclei number as primary or secondary outcomes were considered. Twenty-seven studies incorporating 62 treatment groups and 903 subjects fulfilled the inclusion criteria and were included in the analyses. RESULTS Muscle fiber hypertrophy of ≤10% induces increases in myonuclear content, although a significantly higher number of myonuclei are observed when muscle hypertrophy is ~22%. Additional analyses showed that age, sex, and muscle fiber type do not influence muscle fiber hypertrophy or myonuclei addition. CONCLUSIONS Although a more consistent myonuclei addition occurs when muscle fiber hypertrophy is >22%, our results challenge the concept of a muscle hypertrophy threshold as significant myonuclei addition occurs with lower muscle hypertrophy (i.e., <10%).
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Dietary nitrate-induced increases in human muscle power: high versus low responders.
Coggan, AR, Broadstreet, SR, Mikhalkova, D, Bole, I, Leibowitz, JL, Kadkhodayan, A, Park, S, Thomas, DP, Thies, D, Peterson, LR
Physiological reports. 2018;(2)
Abstract
Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex.
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Protein Supplementation Augments Muscle Fiber Hypertrophy but Does Not Modulate Satellite Cell Content During Prolonged Resistance-Type Exercise Training in Frail Elderly.
Dirks, ML, Tieland, M, Verdijk, LB, Losen, M, Nilwik, R, Mensink, M, de Groot, LCPGM, van Loon, LJC
Journal of the American Medical Directors Association. 2017;(7):608-615
Abstract
OBJECTIVE Protein supplementation increases gains in lean body mass following prolonged resistance-type exercise training in frail older adults. We assessed whether the greater increase in lean body mass can be attributed to muscle fiber type specific hypertrophy with concomitant changes in satellite cell (SC) content. DESIGN A total of 34 frail elderly individuals (77 ± 1 years, n = 12 male adults) participated in this randomized, double-blind, placebo-controlled trial with 2 arms in parallel. INTERVENTION Participants performed 24 weeks of progressive resistance-type exercise training (2 sessions per week) during which they were supplemented twice-daily with milk protein (2 × 15 g) or a placebo. METHODS Muscle biopsies were taken at baseline, and after 12 and 24 weeks of intervention, to determine type I and type II muscle fiber specific cross-sectional area (CSA), SC content, and myocellular characteristics. RESULTS In the placebo group, a trend for a 20% ± 11% increase in muscle fiber CSA was observed in type II fibers only (P = .051), with no increase in type I muscle fiber CSA. In the protein group, type I and II muscle fiber CSA increased by 23% ± 7% and 34% ± 10% following 6 months of training, respectively (P < .01). Myonuclear domain size increased over time in both groups and fiber types (P < .001), with no significant differences between groups (P > .05). No changes in myonuclear content and SC contents were observed over time in either group (both P > .05). Regression analysis showed that changes in myonuclear content and domain size are predictive of muscle fiber hypertrophy. CONCLUSIONS Protein supplementation augments muscle fiber hypertrophy following prolonged resistance-type exercise training in frail older people, without changes in myonuclear and SC content.
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Na,K-ATPase regulation in skeletal muscle.
Pirkmajer, S, Chibalin, AV
American journal of physiology. Endocrinology and metabolism. 2016;(1):E1-E31
Abstract
Skeletal muscle contains one of the largest and the most dynamic pools of Na,K-ATPase (NKA) in the body. Under resting conditions, NKA in skeletal muscle operates at only a fraction of maximal pumping capacity, but it can be markedly activated when demands for ion transport increase, such as during exercise or following food intake. Given the size, capacity, and dynamic range of the NKA pool in skeletal muscle, its tight regulation is essential to maintain whole body homeostasis as well as muscle function. To reconcile functional needs of systemic homeostasis with those of skeletal muscle, NKA is regulated in a coordinated manner by extrinsic stimuli, such as hormones and nerve-derived factors, as well as by local stimuli arising in skeletal muscle fibers, such as contractions and muscle energy status. These stimuli regulate NKA acutely by controlling its enzymatic activity and/or its distribution between the plasma membrane and the intracellular storage compartment. They also regulate NKA chronically by controlling NKA gene expression, thus determining total NKA content in skeletal muscle and its maximal pumping capacity. This review focuses on molecular mechanisms that underlie regulation of NKA in skeletal muscle by major extrinsic and local stimuli. Special emphasis is given to stimuli and mechanisms linking regulation of NKA and energy metabolism in skeletal muscle, such as insulin and the energy-sensing AMP-activated protein kinase. Finally, the recently uncovered roles for glutathionylation, nitric oxide, and extracellular K(+) in the regulation of NKA in skeletal muscle are highlighted.