Muscles

  • basic
    • Learning Objectives
      • Understand the composition and structure of skeletal muscles.
      • Know the molecular basis of muscle contraction.
      • Understand the mechanics of muscle contraction and force production in muscle.
      • Know muscle fiber differentiation and muscle remodeling.
    • Muscle Types
      • skeletal muscle骨骼肌
        • Skeletal muscles comprise 40 to 45% of total body weight.
        • attached to bones via tendons肌腱.
        • responsible for locomotion and body motion.
        • under voluntary control.
      • smooth muscle平滑肌
        • Smooth muscle is typically found surrounding the lumen of tubes within the body.
        • Examples include blood vessels, the urinary tract, and the gastrointestinal tract.
        • Smooth muscle controls the caliber of the lumen and generates peristaltic waves.
        • under involuntary control
      • cardiac muscle心肌
        • Cardiac muscle makes up the major bulk of the heart mass.
        • It is sufficiently unique to be considered a different muscle type.
        • under involuntary control
  • Skeletal Muscle
    • Structure and Organization
      • Gross Organization
        • sarcomere→myofibril→muscle fiber+blood vessel+connective tissue→muscle
        • Skeletal muscle is a remarkably efficient and adaptable tissue.
        • Skeletal muscles are typically relatively long and thin, often described as spindle shaped
        • In cross-section, skeletal muscle consists of
          • blood vessels
          • connective tissues
          • muscle fibers肌纤维
            • Individual muscle fibers are long rod-shaped muscle cells
              • 10 to 100 μm in diameter
              • up to 30 cm in length
            • Muscle fibers are typically multinucleated and contain many mitochondria.
            • The most prominent constituent of the muscle fiber is the myofibril肌原纤维.
            • The myofibril is made up of several sarcomeres肌节.
      • Sarcomere Filaments
        • 黑的粗的myosin连着M, 白的细的actin连着Z
        • thick filaments粗肌丝
          • about 15 nm in diameter
          • composed of myosin肌球蛋白
          • located in the central region of the sarcomere
          • their orderly, parallel arrangement gives rise to dark bands
        • thin filaments细肌丝
          • approximately 5 nm in diameter
          • composed of actin肌动蛋白
          • attached at either end of the sarcomere to the Z line
          • The Z line links thin filaments of adjacent sarcomeres and defines the limits of each sarcomere.
          • Thin filaments extend from the Z line toward the center of the sarcomere, where they overlap with thick filaments.
      • Band Nomenclature
        • 收缩时A不变,I变短H变短
        • A band
          • A bands are the thick filaments which are strongly anisotropic.
          • The width of the A band remains constant during sarcomere shortening.
        • I band
          • The I band is bisected by the Z lines.
          • It contains the portion of the thin filaments that does not overlap with the thick filaments.
          • It also contains the elastic part of titin.
          • The I band decreases as the Z lines move closer together during shortening.
        • H zone
          • In the center of the A band, in the gap between the ends of the thin filaments, is the H zone.
          • It is a light band containing only thick filaments and the part of titin integrated in the thick filaments.
        • M line
          • A narrow dark area in the center of the H zone is the M line.
          • It is produced by transversely and longitudinally-oriented proteins that link adjacent thick filaments.
          • It maintains the parallel arrangement of thick filaments.
        • Z line
          • Z lines define the boundaries of each sarcomere.
          • Adjacent sarcomeres share the Z-line linkage of thin filaments.
    • Molecular Basis of Muscle Contraction
      • Sliding Filament Mechanism
        • 本质是myosin head一直扒拉actin
        • Active shortening of the sarcomere, and hence of the muscle, results from relative movement of actin and myosin filaments past one another.
        • Each filament retains its original length during sliding.
        • The force of contraction is developed by the myosin heads, or cross-bridges横桥.
        • Cross-bridges act in the region of overlap between actin and myosin.
        • A single movement of a cross-bridge produces only a small displacement of the actin filament relative to the myosin filament.
        • Each individual cross-bridge detaches from one receptor site on actin and reattaches to another site farther along.
        • The process repeats five or six times.
        • At any given moment only about half of the cross-bridges actively generate force and displacement.
        • When active cross-bridges detach, others take up the task so that shortening is maintained.
        • Sarcomere shortening is reflected as a decrease in the I band, the A band remains constant.
      • Calcium and Excitation-Contraction Coupling
        • 电信号 → 化学信号Ca2+ → 电信号
        • calcium ion Ca2+钙离子
          • 原肌球蛋白会挡住thin filament上与myosin的结合位点,当有Ca2+时,肌钙蛋白会拉着原肌球蛋白移动,露出与myosin的结合位点,肌肉收缩
          • A key to the sliding mechanism is Ca2+, which turns contractile activity on and off.
          • Muscle contraction is initiated when calcium is made available to the contractile elements.
          • Contraction ceases when calcium is removed.
        • sarcolemma肌膜
          • 肌膜的内质网存着Ca2+
          • Mechanisms that regulate calcium availability are coupled to electric events in the muscle membrane.
          • An action potential in the sarcolemma provides the electric signal for initiating contractile activity.
        • excitation-contraction coupling兴奋-收缩耦联
          • The electric signal triggers the chemical events of contraction.
          • When the motor neuron stimulates the muscle at the neuromuscular junction, the propagated action potential depolarizes the sarcolemma.
          • There is an inward spread of the action potential along the system.
      • The Motor Unit
        • 一个神经加上所有控制的muscle fiber算一个单位,一个单位要么最大收缩要么不收缩,一个单位的muscle fiber与其他单位的muscle fiber分散在整个肌肉中,而不是一坨
        • The functional unit of skeletal muscle is the motor unit运动单位.
        • A motor unit includes
          • a single motor neuron
          • all of the muscle fibers innervated by it
        • This unit is the smallest part of the muscle that can be made to contract independently.
        • When stimulated, all muscle fibers in the motor unit respond as one.
        • The fibers of a motor unit show an all-or-none response全或无反应.
        • The number of muscle fibers forming a motor unit is closely related to the degree of control required of the muscle.
        • Fibers of each motor unit are not contiguous but dispersed throughout the muscle with fibers of other units.
        • If a single motor unit is stimulated, a large portion of the muscle appears to contract.
        • If additional motor units are stimulated, the muscle contracts with greater force.
    • The Musculotendinous Unit肌腱单位 and Hill’s Model
      • 总结
      • Viscoelastic Structures
        • Tendons and connective tissues in and around the muscle belly are viscoelastic structures.
        • They help determine the mechanical characteristics of entire muscle during contraction and passive extension.
        • 分为收缩成分和弹性成分
          • contractile component
            • the contractile proteins of the myofibril, actin, and myosin
          • elastic component
            • tendons
              • represent a spring-like elastic component located in a series with the contractile component
            • connective tissues
              • epimysium肌外膜
              • perimysium肌束膜
              • endomysium肌内膜
              • sarcolemma肌膜
              • represent an elastic component located parallel to the contractile component
      • Hill-Type Muscle Model
        • Hill-type muscle model (Hill’s model) is one of the most used models to describe the mechanism of force production.
        • It describes the behavior of the muscle and tendon using different elements.
        • Hill model tree separates CC, SEC, and PEC
        • contractile component CC收缩元件
          • represents the fundamental mechanical behavior of the sarcomere
          • governed by activation kinetics, force-length properties, and force-velocity properties
          • corresponds to overlap of actin and myosin
          • produces active tension主动张力
        • series elastic component SEC串联弹性元件
          • influence force, length, and speed of the entire unit
          • connective tissues within the tendon
          • smoothen out the rapid changes in muscle tension
          • contributes to passive tension被动张力
        • parallel elastic component PEC并联弹性元件
          • influence force, length, and speed of the entire unit
          • parallel connective tissues
          • mainly produces passive tension
      • Elastic Component Function
        • 弹性成分可以储存然后释放能量
        • When parallel and series elastic components stretch during active contraction or passive extension, tension is produced and energy is stored.
        • When they recoil with muscle relaxation, this energy is released.
        • Their distensibility and elasticity are valuable in several ways
          • keep the muscle in readiness for contraction
          • ensure that muscle tension is produced and transmitted smoothly during contraction
          • ensure that contractile elements return to their original (resting) positions when contraction is terminated
          • help prevent passive overstretch of relaxed contractile elements
          • absorb energy proportional to the rate of force application, dissipate energy in a time-dependent manner
    • Types and Performance of Muscle Contraction
      • Types of Muscle Contraction
        • dynamic work动态做功
          • Mechanical work is performed and joint motion is produced.
          • concentric contraction向心收缩
            • Muscles develop sufficient tension to overcome the resistance of the body segment.
            • The muscles shorten and cause joint movement.
            • The net moment generated by the muscle is in the same direction as the change in joint angle.
          • eccentric contraction离心收缩
            • A muscle cannot develop sufficient tension and is overcome by the external load.
            • The muscle progressively lengthens instead of shortening.
            • The net muscle moment is in the opposite direction from the change in joint angle.
            • One purpose of eccentric contraction is to decelerate the motion of a joint.
        • static work静态维持
          • No mechanical work is performed.
          • Posture or joint position is maintained.
          • isometric contraction等长收缩
            • The muscle attempts to shorten, but it does not overcome the load and cause movement.
            • Myofibrils shorten and stretch the series elastic component, thereby producing tension.
            • No change takes place in the distance between the muscle’s points of attachment.
            • The muscle produces a moment that supports the load in a fixed position, for example maintains posture.
          • Although no motion and no mechanical work occur during isometric contraction, physiologic work is performed.
          • Energy is expended and mostly dissipated as heat, called isometric heat production.
      • Length-Tension Relationship
        • The force, or tension, that a muscle exerts varies with the length at which it is held when stimulated.
        • Maximal tension
          • produced when the muscle fiber is approximately at its slack, or resting, length.
          • 2.0-2.25 μm sarcomere length
          • If the fiber is held at shorter lengths, tension falls off slowly at first and then rapidly.
          • If the fiber is lengthened beyond resting length, tension progressively decreases.
        • Whole muscle isometric length-tension
          • Tension produced by both active components and passive components must be taken into account.
          • active tension主动张力
            • developed by the contractile elements of the muscle
            • resembles the curve for the individual fiber
          • passive tension被动张力
            • developed when the muscle surpasses its resting length
            • the noncontractile muscle belly is stretched
            • mainly developed in the parallel and series elastic components
          • total tension总张力
            • combined effect of active tension and passive tension
            • At longer whole-muscle lengths, passive tension can raise total tension even while active tension declines.
      • Load-Velocity Relationship
        • 东西从0变重速度减小,到0之后再变重肌肉就离心收缩了
        • The velocity of shortening of a muscle contracting concentrically is inversely related to the external load applied.
        • When the external load equals the maximal force that the muscle can exert, the velocity of shortening becomes zero.
        • At zero shortening velocity, the muscle contracts isometrically.
        • When the load is increased still further, the muscle contracts eccentrically, the muscle elongates during contraction.
        • The load-velocity relationship is reversed from that of the concentrically contracting muscle.
        • The muscle eccentrically lengthens more quickly with increasing load.
      • Force-Time Relationship
        • 收缩很快,传递需要时间
        • The force, or tension, generated by a muscle is proportional to the contraction time.
        • The longer the contraction time, the greater the force developed, up to maximum tension.
        • Time is allowed for tension produced by contractile elements to be transmitted through elastic components to the tendon.
        • Tension production in the contractile component can reach a maximum in as little as 10 msec.
        • Up to 300 msec may be needed for that tension to be transferred to the elastic components.
        • The tendon reaches maximum tension only if the active contraction process is of sufficient duration.
    • Factors
      • Effect of Skeletal Muscle Architecture
        • The more sarcomeres lie in series, the longer the myofibril.
        • The more sarcomeres lie parallel, the larger the cross-sectional area of the myofibril.
        • Two architectural patterns affect contractile properties
          • long myofibrils
            • velocity and excursion, or working range, are proportional to myofibril length
            • designed for excursion and velocity
          • thick myofibrils
            • force is proportional to cross-sectional area
            • shorter fibers and larger cross-sectional area are designed to produce force
        • 图 - short fibers with large PCSA show higher force, long fibers with small PCSA show larger range and velocity
      • Effect of Temperature
        • Changes in temperature affect the contractile properties of skeletal muscles.
        • Extreme environmental conditions change the rate of enzymatic activity within the muscle.
        • 升温
          • A rise in muscle temperature causes an increase in conduction velocity across the sarcolemma.
          • Increased conduction velocity increases the frequency of stimulation and hence production of muscle force.
        • 降温
          • With a decrease in temperature, there is a decrease in production or utilization of ATP.
          • Cooling can deplete intracellular glycogen and affect muscle performance power.
      • Effect of Fatigue
        • ATP availability
          • 肌肉收缩和放松依赖ATP，低频刺激下，若氧气和营养充足，肌肉可长时间工作，前提是ATP合成速率能跟上分解速率
          • The ability of a muscle to contract and relax depends on the availability of ATP.
          • If oxygen and nutrients are adequate, muscle can sustain low-frequency twitch抽搐 responses for a long time.
          • The frequency must be low enough for ATP synthesis to keep up with ATP breakdown during contraction.
        • oxidative phosphorylation氧化磷酸化
          • 中强度活动时主要靠此途径供能，但剧烈运动时ATP分解太快，即使氧气充足，氧化磷酸化速度也可能不足
          • At moderate rates of muscle activity, most required ATP can be formed by oxidative phosphorylation.
          • During very intense exercise, ATP is broken down very rapidly.
          • The ability to replace ATP by oxidative phosphorylation may be limited by inadequate oxygen delivery.
          • Even when oxygen delivery is adequate, oxidative phosphorylation may be too slow to sustain very intense exercise.
        • anaerobic glycolysis无氧糖酵解
          • 剧烈运动时该途径贡献增加，其优点是反应快、无需氧气，缺点是每分子葡萄糖产生的ATP很少，且产生乳酸，会快速消耗糖原，当肌球蛋白ATP酶分解ATP的速度超过糖酵解合成速度时，ATP浓度下降，疲劳迅速发生
          • Anaerobic glycolysis contributes an increasing portion of ATP during intense exercise.
          • It produces much smaller amounts of ATP from glucose breakdown.
          • It operates at a much faster rate.
          • It can proceed in the absence of oxygen, with lactic acid as its end product.
          • It requires large amounts of glucose for small amounts of ATP.
          • Existing glycogen supplies may be depleted quickly when activity is intense.
          • Myosin ATPase may break down ATP faster than glycolysis can replace it, and fatigue occurs rapidly as ATP concentrations drop.
        • Recovery and efficiency
          • 运动后需要重新合成磷酸肌酸和糖原，期间耗氧量仍较高，化学能转化为机械能的效率通常只有20%-25%，大部分能量变成热量，最高状态下也仅约45%的能量用于收缩
          • After intense exercise, creatine phosphate磷酸计算 levels drop.
          • Much of the muscle glycogen may have been converted to lactic acid乳酸.
          • Creatine phosphate must be resynthesized and glycogen stores must be replaced.
          • Both processes require energy, so the muscle continues to consume oxygen rapidly even after contraction stops.
          • Chemical energy to movement efficiency is usually no more than 20% to 25%.
          • Most energy is dissipated as heat.
          • Even in its most efficient state, a maximum of only about 45% of energy is used for contraction.
      • Muscle Damage
        • mechanical model力学模型
          • 强调离心收缩产生更大的力，使每个横桥承受的张力增加，导致收缩蛋白更容易发生结构破坏，该模型主要适用于由离心收缩引起的运动损伤（如冲刺、跳跃、下坡跑等）
          • Eccentric contraction produces a greater amount of force.
          • This increases force per cross-bridge and predisposes contractile proteins to fail.
          • It is primarily true with exercise-induced injuries involving eccentric muscle contraction.
        • metabolic model代谢模型
          • 关注肌肉在受力状态下的代谢紊乱——钙离子（Ca²⁺）水平升高，引发肌纤维退化，该模型主要解释以向心收缩为主的活动（如长距离自行车、马拉松）所导致的肌肉损伤，认为损伤更多源于代谢产物堆积和钙稳态失衡，而非直接的机械撕裂
          • Deficiencies occur within the stressed muscle.
          • The presence of Ca2+ increases and may result in muscle fiber degeneration.
          • This may explain muscle damage from activities primarily involving concentric contraction.
          • Examples include long cycling events or marathons.
      • Effect of Disuse and Immobilization
        • Disuse and immobilization have detrimental effects on muscle fibers.
        • Main effects include
          • loss of endurance and force production
          • muscle atrophy萎缩 at microstructural and macrostructural levels
        • These effects depend on
          • fiber type
          • muscle length during immobilization
          • cause of immobilization
        • immobilization cause
          • Loss of muscle force production due to reduced physical activity and biologic aging.
          • loss of strength is greater in the lower limbs than in the upper limbs.
          • Reduced postural demand leads to atrophy减少 of slow twitch fibers慢肌纤维. Slow twitch fiber atrophy results in difficulties in postural maintenance. Their cross-sectional area decreases. Their potential for oxidative enzyme activity is reduced.
        • Prevention and Recovery
          • Physical training increases the cross-sectional area of all muscle fibers.
          • The affected fiber type depends on the chosen sport.
            • In endurance athletes, slow twitch fibers are mainly affected.
            • In explosive activities such as sprinting短跑, intermediate twitch fibers中间型肌纤维 are affected.
          • Early motion may prevent this atrophy
          • Electric stimulation may also prevent
            • the decrease in slow twitch fiber size
            • the decline in oxidative enzyme activity caused by immobilization
      • Effects of Physical Training
        • Physical activity influences muscle architecture and force production.
        • Fascicle length肌束长度 differs in highly trained athletes, lesser trained athletes, and untrained controls.
        • Unique muscle geometry can be found in athletes from different sports.
          • sprinter 短跑运动员
          • endurance runner 耐力跑运动员
          • weightlifter 举重运动员
        • There was no relative or absolute difference of fascicle length between gender.
        • Athlete comparison table
          • 图
          • Muscles compared include rectus femoris, vastus medialis, vastus lateralis, tibialis anterior, medial head of gastrocnemius, and lateral head of gastrocnemius.
          • Sports compared include boxing, judo, taekwondo, soccer, and wrestling.
          • Variables include MT (mm), FA (°), maximum anaerobic power, and mean anaerobic power.
        • Training type and fiber type
          • Different exercises have different effects on different types of muscle fiber.
          • Intermediate twitch fibers and fast twitch fibers show greater enlargement after eccentric training than after concentric training. This is in line with increased isometric force production.
          • Physical activity influences differentiation into slow-twitch and fast-twitch fiber, which may change the biomechanical properties of force production.
          • The cross-sectional area of the fibers is affected by one’s principal activity.
          • In endurance athletes, the area taken up by slow twitch fibers and intermediate twitch fibers increases. This increase occurs at the expense of the total area of fast twitch fibers.
  • Take-Home Message
    • What are the thick filaments and thin filaments, respectively?
      • Thick filaments are about 15 nm in diameter and composed of myosin.
      • Thin filaments are approximately 5 nm in diameter and composed of actin.
      • Thin filaments are attached to Z lines and overlap with thick filaments toward the center of the sarcomere.
    • What are Z line, A band, I band, H zone, and M line?
      • Z line defines the limits of each sarcomere and links thin filaments of adjacent sarcomeres.
      • A band corresponds to thick filaments and remains constant during shortening.
      • I band contains non-overlapping thin filaments and elastic titin; it decreases during shortening.
      • H zone is the central light region of the A band containing only thick filaments.
      • M line is the central dark line that links adjacent thick filaments and maintains parallel arrangement.
    • What is the Hill’s model?
      • A muscle force-production model composed of CC, SEC, PEC, and tendon-related behavior.
      • CC represents sarcomere contractile behavior and active tension.
      • SEC represents series elasticity, mainly tendon connective tissues.
      • PEC represents parallel connective tissues and passive tension.
      • The model links activation kinetics, force-length properties, and force-velocity properties.
    • What is the length-tension relationship in muscle fiber?
      • Muscle tension varies with the length at which the fiber is held when stimulated.
      • Maximal active tension occurs near resting sarcomere length, about 2.0-2.25 μm.
      • Shorter or longer sarcomere lengths reduce active tension because actin-myosin overlap becomes less optimal.
      • In whole muscle, total tension includes active tension plus passive tension from elastic components.
    • How does disuse and immobilization affect muscle force and muscle composition?
      • They reduce endurance and force production.
      • They cause muscle atrophy at microstructural and macrostructural levels.
      • Loss of strength is greater in lower limbs than upper limbs.
      • Prolonged bed rest especially causes slow twitch fiber atrophy and reduced oxidative enzyme activity.
      • Early motion and electric stimulation may help prevent atrophy.