Chapter 44 Skeletal Muscle Tommy Boone, PhD, MPH, FASEP, EPC     The most abundant tissue in the body is skeletal muscle.  Accounting for approximately 40% of the body weight, a person weighing 70 kg (154 lb) has close to 28 kg (61.6 lb) of lean muscle tissue.  Of the more than 400 skeletal muscles, 75 make up the upper and lower extremities.  They are found in pairs on the right and left sides of the body.  There are several purposes of the muscles.  Aside from creating motion across joints throughout the body, muscles help to protect the skeletal system and the organs contained within them.  Skeletal muscles perform specific motions across different joints in response to nerve messages from the central nervous system transmitted through the peripheral nervous system. Organization of Muscle The epimysium, a fibrous connective tissue fascia, surrounds individual muscles, which are composed of fascicles of fibers organized into various-sized bundles.  The fascicles are encased in connective tissue sheath, the perimysium.  Each muscle fiber is encased by connective tissue called the endomysium.  Beneath the endomysium is the sarcolemma.  This elastic sheath has infoldings that invaginate the fiber interior.  All the different connective tissues extend beyond the muscle to contribute to tendons.  Muscles are attached to bones by tendons.  Skeletal muscle is best recognized at the structural unit level as a long cylindrical cell or fiber.  Each muscle consists of strands of myofibrils.  All myofibrils are composed of smaller myofilaments (actin and myosin) that give rise to a repeating pattern along the length of the myofibril.  Individual contractile units called sarcomeres constitute the organization of thick (myosin) and thin (actin) filaments.  Myosin is located in the central region of the sarcomere, where they give rise to the A bands.  The actin proteins give rise to the I band.  They are attached at one end to the transverse tubules (known as the Z line) that originate with the infoldings at the surface of the fiber.  The rest of the filament is free to interact with the cross-bridges that extend from the myosin proteins, which are surrounded by six equally spaced thin filaments on each end.  The cross-bridges interdigitate with active actin sites located on the actin molecules that extend into the middle of each sarcomere.  Each actin filament is associated with two additional proteins called tropomyosin and troponin.  They are involved in regulating muscle contraction.  Muscle Contraction According to the sliding filament theory of muscle contraction, individually linked sarcomeres shorten (contract), a condition that results when the filaments slide past each other.  The movement of the actin filaments towards the middle of the sarcomere occurs as the myosin cross-bridges attach themselves to the actin sites.  Muscle contraction (shortening) is reflected in the sarcomere as a decrease in the I band as the Z lines (which are located at the ends of the actin filaments) move closer together.  The width of the A band (the myosin filament) remains unchanged.  Muscle contraction is initiated when calcium is made available within the muscle fiber.  The release of calcium from the sarcoplasmic reticulum (SR), a tubule system within individual fibers that run lengthwise with the fibers, increases the concentration of calcium within the fiber.  This calcium is then used to initiate contraction, given the affinity of troponin to calcium.  As troponin attaches to calcium, it produces a movement of the tropomyosin molecule that frees up the actin site so that the charged cross-bridge can contact the site resulting in the liberation of energy from the adenosine triphosphate (ATP) molecule.  The energy is used to drive the cross-bridge inwardly towards the mid-line of the sarcomere.  This is the reason, therefore, that the Z lines are required to move to the middle of the myosin filament. The release of calcium from the SR system is linked directly to the nervous system.  As an example, with contraction of the biceps brachii, nerve impulses are sent from the motor cortex of the brain through the spinal cord.  At the level of C5-7, the peripheral nervous system is activated.  The musculocutaneous nerve continues the wave of axon depolarization to individual muscle fibers via motor units.  Each motor unit has “x” number of motor nerves that extend to individual muscle fibers by way of a neuromuscular junction (also called synapse).  The electric events at the synapse initiate the stepwise actions that result in muscle contraction (otherwise known as excitation-contraction coupling). When the motor nerve is depolarized, acetylcholine is released from the axon terminals at the neuromuscular junction.  The acetylcholine binds to the receptor sites on the motor end plate membrane (a specialized connecting point of the muscle’s sarcolemma with the axon terminal).  The neurotransmitter, acetylcholine, increases the motor end plate’s permeability to sodium and potassium ions, which produces an end-plate potential.  This potential depolarizes the sarcolemma that creates a muscle action potential that is propagated throughout the muscle membrane causing depolarization of the transverse tubules.  This leads to the release of calcium from the terminal cisternae of the sarcoplasmic reticulum.  Calcium binds to troponin, which is responsible for the movement of tropomyosin away from the actin receptor site.  The myosin cross-bridges then bind to the actin filament. Actin activates the myosin ATPase found on the myosin cross-bridge.  ATP (the energy currency of the muscle fiber) is hydrolyzed to adenosine diphosphate (ADP) and phosphate.  The splitting of ATP releases stored energy to produce movement of the myosin cross-bridges, which produces sliding of the thick and thin filaments past each other.  Then, breaking of the actin-myosin connection to allow for another actin combination with myosin requires another ATP on the myosin cross-bridge.  Cycling of binding and unbinding of actin with myosin cross-bridges along the actin filament is continued with high sarcoplasmic concentration of calcium.  With a decrease in the depolarization of the motor axon, there is less acetylcholine released to initiate the excitation-contraction coupling steps.  As the transverse tubules depolarize less frequently, there is less a direct effect on the release of calcium ions from the sarcoplasmic reticulum surrounding the myofibrils.  The concentrations of calcium ions fall as they are pumped into the sarcoplasmic reticulum.  The result is that calcium dissociates from troponin, thus allowing tropomyosin to keep the myosin cross-bridges from connecting with the actin receptor sites.  The actin filament slides back, the sarcomere lengthens, and the muscle fiber relaxes. The Role of the Nervous System in Muscle Contraction Muscles are robots ready to contract when a nerve impulse initiates the excitation-contraction coupling.  Without the direct connection of nerves, muscles do not contract (at least not voluntarily).  An injury to a nerve that results in either a loss of motion or significantly reduced motion can take place at the pre-central gyrus of the motor cortex of the frontal lobe or throughout the length of either the axon of the upper motor neuron (i.e., brain and spinal cord) or the axon of the lower motor neuron (peripheral nerves).  In other words, an injury could involve the central nervous system or the peripheral nervous system; the latter being defined specifically by the brachial plexus (nerves the upper body) and the lumbar-sacral plexuses (nerves to the lower body). As an example, the peripheral nerve responsible for initiating muscle contraction of the biceps brachii to flex the elbow and shoulder joints is the musculocutaneous nerve.  This nerve is part of the brachial plexus.  Although the descending pathway (i.e., the lateral corticospinal track) of motor nerves from the brain is working fine, an injury to the spinal cord at the anterior horn level might be expected to involve the spinal contributions to the shoulder flexor nerve(s).  This would result in either a loss of the nerve (and other nerves to the upper limb) or a decrease in the force of contraction of the biceps brachii.  The integrity of the nervous system is critical to the functioning of the skeletal muscle. Regarding the biceps brachii, as an example, on average there are 500,000 muscle fibers.  This number is present at birth and remains essentially unchanged throughout life.  With growth of the muscles during puberty or during athletics, the increase in the size of the muscles result from the increase in myofibrils.  The number of muscle fibers does not increase with age or muscular training.  On average, each muscle fiber contains 2000 myofibrils, and each myofibril contains on average 2000 myofilaments.  The muscle is anchored superiorly at two points: the long head arises from the supraglenoid tubule and the short head arises from the coracoid process).  It inserts on the radial tuberosity of the lateral forearm bone.  When it contracts at the shoulder joint, the short head produces flexion, inward rotation, and adduction.  The long head produces shoulder flexion, inward rotation, and abduction.  At the elbow joint, both heads produce flexion and, if necessary or required, supination of the forearm and hand. The specific motions are guided by the need for graded contractions.  The motor unit, which comprises a single motor nerve and all of the muscle fibers innervated by it, controls the graded response.  With reference to the biceps brachii, a single motor unit may innervate on average 150 fibers.  This means that the muscle has approximately 3,300 motor units.  Hence, the number of motor unit involvement during contraction defines the intensity of contraction.  Since a muscle fiber can only contract all-or-none, given the interconnectedness of the myofibrils within the fiber, a nerve impulse through a nerve that innervates 150 fibers results in 100% contraction of at least 150 muscle fibers.  The contraction results in a certain increase in power that is used to overcome the inertia of the musculoskeletal mass.  If additional force is required to lift a greater mass or to move the resistance through a determined range of motion with increased velocity, then more motor units must be initiated via the motor cortex of the brain.  By increasing the number of motor units activated at a given time, both the quality of the contraction and the precision of the motion are increased.  The increased recruitment of motion units is consistent with great force and, thus the display of strength. Types of Muscle Contraction The muscle tension that is developed during contraction is the result of many factors.  One is the points of attachment to the skeletal system.  As long as the muscle is attached at both ends of its length to bone or fascia, it can create a force to overcome a resistance or load.  Using the biceps brachii example again, if the shoulder joint is held essentially vertical to the ground, the elbow joint will flex when it contracts.  On the other hand, when the load is returned to the original position, the same muscle (along with others) contract to lower it safely under the influence of gravity.  Here, the muscle is contracting but differently from when the load was raised.  The first involves shortening of the muscle at varying velocities and tension, which is called concentric muscle contraction.  Concentric contraction occurs when there is a need to overcome a load under the influence of gravity.  The second type of contraction occurs when a movement has been created, as in an elbow curl of 30 lb, and now the weight is returned to the original position.  This type of contraction involves lengthening of the biceps brachii, which is called eccentric contraction.  The contraction determines how fast the weight is lowered under the influence of gravity and, therefore, serves to protect the joint from injury.  Both types of muscle work and contraction are generally referred to as isotonic muscle contraction.  On the other hand, when a muscle contracts without joint movement, the myofibrils undergo shortening in opposition to the load but the muscle does not shorten.  Since the points of attachment (i.e., origin and insertion) of the muscle do not move closer to each other, which is the case with isotonic work, this third type of muscle work is considered a static or isometric contraction.  The fourth type of muscle work is an isokinetic contraction.  Contrary to isotonic work, isokinetic work occurs when the movement of a joint is kept at a constant velocity.  The velocity of contraction is therefore constant resulting in maximal muscle turning effect (torque). Types of Muscle Fibers On the basis of differing contractile and metabolic properties, all muscle fibers are not of the same type.  They differ in a multitude of ways, but primarily by the metabolic pathways used to develop energy (ATP) for muscle contraction.  This raises the interesting point that a certain type of fiber is better than another type in producing energy for contraction.  Since energy is the key to contraction and since contraction is the key to human performance, it stands to reason that having the fiber type that produces the greatest amount of energy for long bouts of exercise increases the chance of performing well.  The converse would appear to be true for the fiber type that produces the greatest amount of energy for short periods of high intensity effort.  Hence, given the genetic predisposition to different fiber types and the desire to perform well in different types of sports, it is important to acknowledge not only the three sources that supply ATP (e.g., creatine phosphate, oxidative phosphorylation in the mitochrondria, and substrate phosphorylation during anaerobic glycolysis) to the infrastructure of each muscle fiber but also the three fiber types: (1) type I, slow-twitch oxidative fibers; (2) type IIA, fast-twitch oxidative-glycolytic fibers; and (3) type IIB, fast-twitch glycolytic fibers. The slow-twitch oxidative fibers (type I) are characterized by a high activity of oxidative phosphorylation.  Even when the exercise intensity is high for prolonged periods of time, the infrastructure of the type I fiber is designed to ensure that adequate ATP is produced to fuel muscle contraction without a significant increase in anaerobic glycolysis.  The fiber’s ability to replace ATP by oxidative phosphorylation within the mitochondria is the best of the three fiber types for at least two primary reasons.  First, type I fibers are generally associated with the propensity for a well developed cardiorespiratory system that helps to ensure there is an adequate delivery of oxygen to the muscle.  Second, because the energy making machinery within the fiber is designed to replace very rapidly the break down of ATP.  Another reason includes a low activity of myosin ATPase at the sarcomere level, thus setting the stage for a slightly slower contraction time.  The net effect is a propensity for pyruvic acid moving smoothly from the sarcoplasm into the high content of mitochondria and, subsequently, as the Kreb’s cycle completes its cycle, the hydrogen ions and carbon dioxide molecules move with ease into the electron transport system and into the venous blood, respectively.  There is little chance of the hydrogen carrier NAD giving the hydrogen ions to pyruvic acid, thus converting it to lactic acid.  Still, another reason for the high oxidative (aerobic) properties include the facilitated blood flow to the active type I fibers due to the high rate of blood flow (i.e., cardiac output) and higher number of capillaries to the fibers.  Type IIA (fast-twitch oxidative-glycolytic) fibers are intermediate muscle fibers between type I and type IIB (fast-twitch glycolytic) fibers.  Individuals with a high level of type IIA muscle fibers have the propensity to perform well in sports in which there is the need for both aerobic (oxidative) and anaerobic (glycolytic) metabolism.  The well-developed aerobic capacity coupled with the fast contraction time ensures a high production of tension for relatively long exercise periods.  However, if the activity demands a higher rate of ATP than can supplied by oxidative phosphorylation, the rate of glycolysis is increased resulting eventually in fatigue.  The fast-twitch glycolytic (type IIB) muscle fibers rely primarily on anaerobic metabolism for muscle contraction.  Few capillaries to the active fibers along with little myoglobin to facilitate oxygen movement within the fibers predisposes ATP production to primarily non-aerobic processes.  The result is that the fibers fatigue easily because the glycogen is quickly depleted.  The poor supply of oxygen to the fibers under high intensity short duration activities hastens the conversion of pyruvic acid to lactate.    Selected Readings Banker, B.Q. 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