🏃Exercise Physiology Unit 3 – Skeletal Muscle Physiology

Key Concepts and Terminology

• Skeletal muscle tissue consists of long, cylindrical cells called muscle fibers that contain multiple nuclei and are specialized for contraction
• Sarcomeres are the basic functional units of muscle fibers, composed of thick (myosin) and thin (actin) filaments that slide past each other during contraction
• Motor units include a single motor neuron and all the muscle fibers it innervates, allowing for precise control of muscle force production
• Excitation-contraction coupling is the process by which an action potential in the motor neuron triggers muscle contraction
• Adenosine triphosphate (ATP) serves as the primary energy source for muscle contraction, with creatine phosphate (CP) providing a rapid reserve
• Muscle fatigue occurs when a muscle can no longer generate the required force or power output due to factors such as depletion of energy stores or accumulation of metabolic byproducts
• Muscle hypertrophy refers to an increase in muscle size and cross-sectional area in response to resistance training, while atrophy is a decrease in muscle size due to disuse or disease

Muscle Structure and Organization

• Skeletal muscles are composed of bundles of muscle fibers called fascicles, which are surrounded by connective tissue layers (endomysium, perimysium, and epimysium)
• Muscle fibers contain numerous myofibrils, which are long, cylindrical structures composed of repeating units called sarcomeres
• Each sarcomere contains thick filaments made of myosin and thin filaments made of actin, along with regulatory proteins such as troponin and tropomyosin
• The arrangement of thick and thin filaments gives skeletal muscle its striated appearance, with dark A-bands (containing myosin) and light I-bands (containing actin)
• Z-lines demarcate the boundaries of each sarcomere and serve as attachment points for the thin filaments
• The sarcoplasmic reticulum is a specialized endoplasmic reticulum that surrounds each myofibril and stores calcium ions necessary for muscle contraction
• Transverse tubules (T-tubules) are invaginations of the muscle fiber membrane that run perpendicular to the myofibrils and allow for rapid transmission of action potentials into the interior of the fiber

Neuromuscular Junction and Muscle Activation

• The neuromuscular junction (NMJ) is the synapse between a motor neuron and a muscle fiber, allowing for the transmission of signals that initiate muscle contraction
• The motor neuron releases the neurotransmitter acetylcholine (ACh) into the synaptic cleft, which binds to nicotinic acetylcholine receptors (nAChRs) on the muscle fiber membrane
• Binding of ACh to nAChRs causes the receptors to open, allowing an influx of sodium ions that depolarizes the muscle fiber membrane and generates an action potential
• The action potential propagates along the muscle fiber membrane and into the T-tubules, triggering the release of calcium ions from the sarcoplasmic reticulum
• Calcium ions bind to troponin, causing a conformational change that moves tropomyosin and exposes the binding sites for myosin on the actin filaments
• Acetylcholinesterase (AChE) rapidly breaks down ACh in the synaptic cleft, ensuring that the muscle fiber can relax and respond to subsequent stimuli

Sliding Filament Theory and Muscle Contraction

• The sliding filament theory explains the mechanism of muscle contraction, whereby the thick and thin filaments slide past each other, shortening the sarcomere and generating force
• Myosin heads on the thick filaments bind to exposed sites on the actin thin filaments, forming cross-bridges
• The myosin heads undergo a conformational change (power stroke), pulling the thin filaments towards the center of the sarcomere and shortening the muscle fiber
• ATP binding to the myosin head causes it to detach from actin, and hydrolysis of ATP allows the myosin head to return to its original position, ready for the next cycle
• The repeated formation and breaking of cross-bridges, coupled with the sliding of filaments, results in muscle contraction and force production
• The force generated by a muscle depends on the number of cross-bridges formed, which is influenced by factors such as the level of muscle activation and the length-tension relationship of the sarcomeres
• Muscle relaxation occurs when calcium ions are actively pumped back into the sarcoplasmic reticulum, lowering the concentration of calcium in the sarcoplasm and allowing tropomyosin to block the myosin-binding sites on actin

Energy Systems and Metabolism in Muscle

• Skeletal muscle relies on three main energy systems to produce ATP for contraction: the phosphagen system, glycolysis, and oxidative phosphorylation
• The phosphagen system, which includes the breakdown of creatine phosphate (CP), provides a rapid but limited supply of ATP for high-intensity, short-duration activities (1-10 seconds)
• Glycolysis is the anaerobic breakdown of glucose to pyruvate, which can be further metabolized to lactate, providing ATP for moderate-intensity activities lasting 30 seconds to 2 minutes
• Oxidative phosphorylation, which occurs in the mitochondria, involves the complete breakdown of glucose and fatty acids in the presence of oxygen, supplying ATP for low-intensity, long-duration activities (>2 minutes)
• The relative contribution of each energy system depends on the intensity and duration of the activity, as well as the individual's fitness level and substrate availability
• During exercise, the increased demand for ATP leads to a greater reliance on glycolysis and oxidative phosphorylation, resulting in increased oxygen consumption and carbon dioxide production
• Lactate accumulation during high-intensity exercise can contribute to muscle fatigue, but it also serves as a valuable fuel source for the heart and other oxidative tissues during recovery

Types of Muscle Fibers

• Skeletal muscle fibers are classified into three main types based on their contractile and metabolic properties: Type I (slow-twitch), Type IIa (fast-twitch oxidative), and Type IIx (fast-twitch glycolytic)
• Type I fibers have a slow contraction velocity, high oxidative capacity, and high fatigue resistance, making them well-suited for prolonged, low-intensity activities (long-distance running)
• Type IIa fibers have a fast contraction velocity, high oxidative capacity, and moderate fatigue resistance, allowing them to support moderate-intensity activities (middle-distance running)
• Type IIx fibers have a fast contraction velocity, low oxidative capacity, and low fatigue resistance, making them best suited for high-intensity, short-duration activities (sprinting)
• The proportion of each fiber type varies among individuals and can be influenced by factors such as genetics, age, and training status
• Muscle fibers can exhibit some plasticity, with changes in fiber type composition occurring in response to specific training stimuli (endurance training increasing Type I fibers, resistance training increasing Type II fibers)

Muscle Adaptations to Exercise

• Regular exercise induces a variety of adaptations in skeletal muscle that enhance its functional capacity and resistance to fatigue
• Endurance training leads to increased mitochondrial density and oxidative enzyme activity, improving the muscle's ability to generate ATP through oxidative phosphorylation
• Resistance training promotes muscle hypertrophy, characterized by an increase in the size and number of myofibrils within each muscle fiber, resulting in greater force-generating capacity
• Both endurance and resistance training can lead to increased capillary density, enhancing blood flow and oxygen delivery to the working muscles
• Neuromuscular adaptations, such as increased motor unit recruitment and synchronization, contribute to improved muscle force production and coordination
• Exercise-induced adaptations are specific to the type, intensity, and duration of the training stimulus, emphasizing the importance of tailoring exercise programs to individual goals and needs
• Detraining, or the cessation of regular exercise, can lead to a reversal of many of these adaptations, highlighting the need for consistent and progressive training to maintain muscle function

Clinical Applications and Disorders

• Understanding the structure, function, and adaptations of skeletal muscle is crucial for the prevention, diagnosis, and treatment of various musculoskeletal disorders and chronic diseases
• Sarcopenia, the age-related loss of muscle mass and strength, can be attenuated through regular resistance training and adequate protein intake
• Muscular dystrophies, such as Duchenne muscular dystrophy, are genetic disorders characterized by progressive muscle weakness and wasting due to defects in structural proteins (dystrophin)
• Disuse atrophy, which occurs due to immobilization or prolonged bed rest, can be mitigated through early mobilization and targeted rehabilitation exercises
• Neuromuscular disorders, such as myasthenia gravis, involve impaired transmission of signals at the neuromuscular junction, leading to muscle weakness and fatigue
• Exercise is an effective non-pharmacological intervention for the prevention and management of chronic diseases, such as type 2 diabetes and cardiovascular disease, in part due to its beneficial effects on skeletal muscle metabolism and insulin sensitivity
• The development of targeted therapies and interventions for musculoskeletal disorders relies on a deep understanding of the molecular and cellular mechanisms underlying muscle structure, function, and plasticity