Skeletal muscle: A review of molecular structure and function, in health and disease

Abstract

Decades of research in skeletal muscle physiology have provided multiscale insights into the structural and functional complexity of this important anatomical tissue, designed to accomplish the task of generating contraction, force and movement. Skeletal muscle can be viewed as a biomechanical device with various interacting components including the autonomic nerves for impulse transmission, vasculature for efficient oxygenation, and embedded regulatory and metabolic machinery for maintaining cellular homeostasis. The “omics” revolution has propelled a new era in muscle research, allowing us to discern minute details of molecular cross‐talk required for effective coordination between the myriad interacting components for efficient muscle function. The objective of this review is to provide a systems‐level, comprehensive mapping the molecular mechanisms underlying skeletal muscle structure and function, in health and disease. We begin this review with a focus on molecular mechanisms underlying muscle tissue development (myogenesis), with an emphasis on satellite cells and muscle regeneration. We next review the molecular structure and mechanisms underlying the many structural components of the muscle: neuromuscular junction, sarcomere, cytoskeleton, extracellular matrix, and vasculature surrounding muscle. We highlight aberrant molecular mechanisms and their possible clinical or pathophysiological relevance. We particularly emphasize the impact of environmental stressors (inflammation and oxidative stress) in contributing to muscle pathophysiology including atrophy, hypertrophy, and fibrosis. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Developmental Biology > Developmental Processes in Health and Disease Models of Systems Properties and Processes > Cellular Models

Intramuscular Injection of Combined Calf Blood Compound (CFC) and Homeopathic Drug Tr14 Accelerates Muscle Regeneration In Vivo

“…Regeneration is significantly influenced by the interaction between SCs and their microenvironment [41,42]. The process of regeneration is highly orchestrated and includes the activation and migration of SCs to the site of injury and their proliferation and differentiation into muscle fibers [43]. SCs are located between the sarcolemma of the muscle fiber and the basal lamina and are quiescent (G0 phase) during homeostasis.…”

Force generated by myosin cross-bridges is reduced in myofibrils exposed to ROS/RNS

“…The human body consist of ~35-40% of skeletal muscle relative to body weight (22). Skeletal muscles are essential for our ability to move and one of its major purposes is to produce force (23,24). A given muscle is made of hundreds to thousands of multinucleated muscle fibers bundled together ( Figure.…”

“…A given muscle is made of hundreds to thousands of multinucleated muscle fibers bundled together ( Figure. 1) (23,24). The muscle bundles and the muscle itself are surrounded by connective tissue called the perimysium and epimysium, respectively (24).…”

“…1) (23,24). The muscle bundles and the muscle itself are surrounded by connective tissue called the perimysium and epimysium, respectively (24). Looking further into the structure of each muscle fiber, it can be observed that it consists of thousands of myofibrils (23), which are repeats of thick and thin filaments that form the functional unit called the sarcomere ( Figure. 2) (23).…”

Aldehyde Dehydrogenase 1 isoforms ALDH1A1 and ALDH1A3 are essential for myogenic differentiation

“…Markers for quiescent and activated SCs have been established in experimental studies (Cobb, 2013;Shen et al, 2003), that allow the tracing of proliferation and differentiation processes. Although the in uence of environmental stimuli on myogenic growth and myotube formation has been addressed in several studies (Mukund & Subramaniam, 2020;Pownall et al, 2002), the molecular mechanism of SC activators and regulators has yet not been fully understood.…”