Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

The quest to increase lean body mass is widely pursued by those who lift weights. Research is lacking, however, as to the best approach for maximizing exercise-induced muscle growth. Bodybuilders generally train with moderate loads and fairly short rest intervals that induce high amounts of metabolic stress. Powerlifters, on the other hand, routinely train with high-intensity loads and lengthy rest periods between sets. Although both groups are known to display impressive muscularity, it is not clear which method is superior for hypertrophic gains. It has been shown that many factors mediate the hypertrophic process and that mechanical tension, muscle damage, and metabolic stress all can play a role in exercise-induced muscle growth. Therefore, the purpose of this paper is twofold: (a) to extensively review the literature as to the mechanisms of muscle hypertrophy and their application to exercise training and (b) to draw conclusions from the research as to the optimal protocol for maximizing muscle growth.

/pdf/the-mechanisms-of-muscle-hypertrophy-and-their-application-544z22aglp.pdf

The mechanisms of muscle hypertrophy and their application to resistance training.

The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a property thathas clinical manifestations and alters muscle function. Here, we review the structure, composition, and mechanical properties of skeletal muscle ECM, describe the cells that contribute to the maintenance of the ECM and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure-function relationships. Detailed structure-function relationships of the ECM have yet to be defined and, as a result, we propose areas for future studies.

Structure and function of the skeletal muscle extracellular matrix

Physical activity relies on muscular force. In adult skeletal muscle, force results from the contraction of postmitotic, multinucleated myofibres of different contractile and metabolic properties. Myofibres can adapt to (patho-)physiological conditions of altered functional demand by radial growth, longitudinal growth, and regulation of fibre type functional gene modules. The adaptation's specificity depends on the distinct molecular and cellular events triggered by unique combinations of conditional cues. In order to derive effective and tailored exercise prescriptions, it must be determined (1) which mechano-biological condition leads to what molecular/cellular response, and (2) how this molecular/cellular response relates to the structural, contractile, and metabolic adaptation. It follows that a thorough mechano-biological description of the loading condition is imperative. Unfortunately, the definition of (resistance) exercise conditions in the past and present literature is insufficient. It is classically limited to load magnitude, number of repetitions and sets, rest in-between sets, number of interventions/week, and training period. In this review, we show why the current description is insufficient, and identify new determinants of quantitative and/or qualitative effects on skeletal muscle with respect to resistance exercise in healthy, adult humans. These new mandatory determinants comprise the fractional and temporal distribution of the contraction modes per repetition, duration of one repetition, rest in-between repetitions, time under tension, muscular failure, range of motion, recovery time, and anatomical definition. We strongly recommend to standardise the design and description of all future resistance exercise investigations by using the herein proposed set of 13 mechano-biological determinants (classical and new ones).

/pdf/new-fundamental-resistance-exercise-determinants-of-4kld0dwsa3.pdf

New fundamental resistance exercise determinants of molecular and cellular muscle adaptations

Non-technical summary
Muscle spasticity, due to an upper motoneuron lesion, often leads to muscle contractures that limit range of motion and cause increased muscle stiffness. However, the elements responsible for this muscle adaption are unknown. Here we show that muscle tissue is stiffer in contracture compared to age-matched children, implicating the extracellular matrix (ECM). However, titin, the major load-bearing protein within muscle fibres, is not altered in contracture, and individual fibre stiffness is unaltered. Increased ECM stiffness is even more functionally significant given our finding of long in vivo sarcomeres which leads to much larger in vivo forces in muscle contracture. These results may lead to novel therapeutics for treating spastic muscle contracture.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2010.203364

Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length

The active and passive contractile performance of skeletal muscle fibers largely depends on the myosin heavy chain (MHC) isoform and the stiffness of the titin spring, respectively. Open questions concern the relationship between titin-based stiffness and active contractile parameters, and titin's importance for total passive muscle stiffness. Here, a large set of adult rabbit muscles ( n = 37) was studied for titin size diversity, passive mechanical properties, and possible correlations with the fiber/MHC composition. Titin isoform analyses showed sizes between ∼3300 and 3700 kD; 31 muscles contained a single isoform, six muscles coexpressed two isoforms, including the psoas, where individual fibers expressed similar isoform ratios of 30:70 (3.4:3.3 MD). Gel electrophoresis and Western blotting of two other giant muscle proteins, nebulin and obscurin, demonstrated muscle type–dependent size differences of ≤70 kD. Single fiber and single myofibril mechanics performed on a subset of muscles showed inverse relationships between titin size and titin-borne tension. Force measurements on muscle strips suggested that titin-based stiffness is not correlated with total passive stiffness, which is largely determined also by extramyofibrillar structures, particularly collagen. Some muscles have low titin-based stiffness but high total passive stiffness, whereas the opposite is true for other muscles. Plots of titin size versus percentage of fiber type or MHC isoform (I-IIB-IIA-IID) determined by myofibrillar ATPase staining and gel electrophoresis revealed modest correlations with the type I fiber and MHC-I proportions. No relationships were found with the proportions of the different type II fiber/MHC-II subtypes. Titin-based stiffness decreased with the slow fiber/MHC percentage, whereas neither extramyofibrillar nor total passive stiffness depended on the fiber/MHC composition. In conclusion, a low correlation exists between the active and passive mechanical properties of skeletal muscle fibers. Slow muscles usually express long titin(s), predominantly fast muscles can express either short or long titin(s), giving rise to low titin-based stiffness in slow muscles and highly variable stiffness in fast muscles. Titin contributes substantially to total passive stiffness, but this contribution varies greatly among muscles.

Isoform Diversity of Giant Proteins in Relation to Passive and Active Contractile Properties of Rabbit Skeletal Muscles

We present the case of a 31-year-old man who was admitted to our emergency department after injection of 10 ml of methadone into his penis He had a history of drug abuse over the last 15 years and a background of three attempted suicidal episodes with a combination of at least two drugs over the past 12 months The current suicide attempt had serious consequences: He suffered from acute renal and liver failure One previously unreported side effect of methadone is erectile dysfunction following injection into the penis In our case, the patient received vardenafil 10 mg once daily without any signs of functional improvement Ten months after the event, there still was complete erectile dysfunction Language: en

https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.111.015370

Lucas G. Prado

Papers

Isoform Diversity of Giant Proteins in Relation to Passive and Active Contractile Properties of Rabbit Skeletal Muscles

Penile Methadone Injection in Suicidal Intent: Life-Threatening and Fatal for Erectile Function