Myosin head Thick filament FIGURE 50.10 Thick filaments are composed of myosin. (a) Each myosin molecule consists of two polypeptide chains wrapped around each other; at the end of each chain is a globular region referred to as the "head "(b) Thick filaments consist of myosin molecules combined into bundles from which the heads protrude at regular intervals Electron micrographs reveal cross- bridges that extend from the thick to Actin molecules the thin filaments, suggesting a mecha nism that might cause the filaments to slide. To understand how this is accom plished, we have to examine the thick and thin filaments at a molecular level Biochemical studies show that each thick filament is composed of many myosin proteins packed together, and Thin filament every myosin molecule has a"head"re gion that protrudes from the thick fila heads form the cross-bridges seen in Thin filaments are composed of globular actin proteins. Two rows of actin proteins studies also show that each thin filament primarily of many glob actin proteins twisted into a double helix(figure 50. 11). ter of the sarcomere( figure 5012b)in a power stroke. At Therefore, if we were able to see a sarcomere at a molecu- the end of the power stroke, the myosin head binds to a lar level, it would have the structure depicted in figure new molecule of ATP. This allows the head to detach 50.12a. from actin and continue the cross-bridge cycle(figure Before the myosin heads bind to the actin of the thin 50.13), which repeats as long as the muscle is stimulated filaments, they act as aTPase enzymes, splitting ATP into to contract ADP and P;. This activates the heads, "cocking" them so In death, the cell can no longer produce ATP and that they can bind to actin and form cross-bridges. Once a therefore the cross-bridges cannot be broken-this myosin head binds to actin, it undergoes a conformational causes the muscle stiffness of death, or rigor mortis. A liv- (shape)change, pulling the thin filament toward the cen- ing cell, however, always has enough ATP to allow the 1006 Part XIlI Animal Form and Function
Electron micrographs reveal crossbridges that extend from the thick to the thin filaments, suggesting a mechanism that might cause the filaments to slide. To understand how this is accomplished, we have to examine the thick and thin filaments at a molecular level. Biochemical studies show that each thick filament is composed of many myosin proteins packed together, and every myosin molecule has a “head” region that protrudes from the thick filaments (figure 50.10). These myosin heads form the cross-bridges seen in electron micrographs. Biochemical studies also show that each thin filament consists primarily of many globular actin proteins twisted into a double helix (figure 50.11). Therefore, if we were able to see a sarcomere at a molecular level, it would have the structure depicted in figure 50.12a. Before the myosin heads bind to the actin of the thin filaments, they act as ATPase enzymes, splitting ATP into ADP and Pi. This activates the heads, “cocking” them so that they can bind to actin and form cross-bridges. Once a myosin head binds to actin, it undergoes a conformational (shape) change, pulling the thin filament toward the center of the sarcomere (figure 50.12b) in a power stroke. At the end of the power stroke, the myosin head binds to a new molecule of ATP. This allows the head to detach from actin and continue the cross-bridge cycle (figure 50.13), which repeats as long as the muscle is stimulated to contract. In death, the cell can no longer produce ATP and therefore the cross-bridges cannot be broken—this causes the muscle stiffness of death, or rigor mortis. A living cell, however, always has enough ATP to allow the 1006 Part XIII Animal Form and Function Myosin head Myosin molecule (a) (b) Thick filament Myosin head FIGURE 50.10 Thick filaments are composed of myosin. (a) Each myosin molecule consists of two polypeptide chains wrapped around each other; at the end of each chain is a globular region referred to as the “head.” (b) Thick filaments consist of myosin molecules combined into bundles from which the heads protrude at regular intervals. Actin molecules Thin filament FIGURE 50.11 Thin filaments are composed of globular actin proteins. Two rows of actin proteins are twisted together in a helix to produce the thin filaments
Thin filaments(actin) Thick filament( myosin) 89x89o89809 883x888x9b88xg888-x9 (b) FIGURE 50. 12 The interaction of thick and thin filaments in striated muscle sarcomeres The heads on the two ends of the thick filaments are oriented in opposite directions (a), so that the cross-bridges pull the thin filaments and the z lines on each side of the sarcomere toward the center. (b)This sliding of the filaments produces muscle contraction 8×888 Thick filament FIGURE 50.13 The cross-bridge cycle in muscle contraction.(a)With ADP and Pi ATP Cross-bridge attached to the myosin head, (b)the head is in a conformation that can bind to actin and form a cross- bridge (o) Binding causes the myosin head to bent conformation, moving the thin filament along the thick filament( to the left in this diagram)and releasing ADP and P;() Binding ofATPto the head detaches the cross-bridge; cleavage of ATP into ADP and Pi the head into its original conformation, allowing the cycle to myosin heads to detach from actin. How, then, is the cross-bridge cycle arrested so that the muscle can relax Thick and thin filaments are arranged to form The regulation of muscle contraction and rela sarcomeres within the myofibrils. Myosin proteins ation re- omprise the thick filaments, and the heads of the quires additional factors that we will discuss in the next myosin form cross-bridges with the actin proteins of section le thin filaments. atP provides the energy for the oss-bridge cycle and muscle contraction Chapter 50 Locomotion 1007
myosin heads to detach from actin. How, then, is the cross-bridge cycle arrested so that the muscle can relax? The regulation of muscle contraction and relaxation requires additional factors that we will discuss in the next section. Thick and thin filaments are arranged to form sarcomeres within the myofibrils. Myosin proteins comprise the thick filaments, and the heads of the myosin form cross-bridges with the actin proteins of the thin filaments. ATP provides the energy for the cross-bridge cycle and muscle contraction. Chapter 50 Locomotion 1007 Z line Thin filaments (actin) (a) (b) Thick filament (myosin) Cross-bridges FIGURE 50.12 The interaction of thick and thin filaments in striated muscle sarcomeres. The heads on the two ends of the thick filaments are oriented in opposite directions (a), so that the cross-bridges pull the thin filaments and the Z lines on each side of the sarcomere toward the center. (b) This sliding of the filaments produces muscle contraction. Thin filament (actin) Myosin head (a) (b) ATP (d) (c) Thick filament (myosin) Cross-bridge ADP Pi FIGURE 50.13 The cross-bridge cycle in muscle contraction. (a) With ADP and Pi attached to the myosin head, (b) the head is in a conformation that can bind to actin and form a crossbridge. (c) Binding causes the myosin head to assume a more bent conformation, moving the thin filament along the thick filament (to the left in this diagram) and releasing ADP and Pi. (d) Binding of ATP to the head detaches the cross-bridge; cleavage of ATP into ADP and Pi puts the head into its original conformation, allowing the cycle to begin again
The Control of muscle contraction The role of ca*+ in Contraction When a muscle is relaxed its myosin heads are "cocked fatP. but are unable bind to actin. This is because the attachment sites for the Tropomy myosin heads on the actin are physically blocked by other protein, known as tropomyosin, in the thin fila ross-bridges therefore cannot form in the relaxed muscle. and the filaments cannot slide In order to contract a muscle, the tropomyosin must be Binding sites for Troponin mov ed out of that the actin. This requires the function of troponin, a regulatory (a) protein that binds to the tropomyosin. The troponin and tropomyosin form a complex that is regulated by the cal ium ion( Ca**)concentration of the muscle cell cytoplasm When the Cat++ concentration of the muscle cell cyto- plasm is low, tropomyosin inhibits cross-bridge formation Ca++ and the muscle is relaxed (figure 50. 14). When the Ca++ concentration is raised, Ca** binds to troponin. This causes the troponin-tropomyosin complex to be shifted away from the attachment sites for the myosin heads on the actin Cross-bridges can thus form, undergo power strokes, and produce muscle contraction Whe re does le Ca++ come from? Muscle fibers store Binding sites for Ca++ Ca++ in a modified endoplasmic reticulum called a sar coplasmic reticulum, or SR (figure 50. 15). When a muscle fiber is stimulated to contract, an electrical impulse travels into the muscle fiber down invaginations called the trans- FIGURE 50. 14 verse tubules (T tubules). This triggers the release of How calcium controls striated muscle contraction.(a)When he muscle is at rest, a long filament of the protein tropomyosin Cat*+ from the SR. Ca*t then diffuses into the myofibrils, Locks the myosin-binding sites on the actin molecule. Because where it binds to troponin and causes contraction. The myosin is unable to form cross-bridges with actin at these sites, contraction of muscles is regulated by nerve activity, and so muscle contraction cannot occur. (b)When Cat* binds to another nerves must influence the distribution of Cat* in the muscle protein, troponin, the Ca++-troponin complex displaces tropomyosin and exposes the myosin-binding sites on actin, permitting cross-bridges to form and contraction to occur Sarcolemma FIGURE 50.15 The relationship between the myofibrils, transverse tubules, and sarcoplasmic reticulum. Impulses travel down the axon of a otor neuron that synapses with a nuscle fiber. The impulses are onducted along the transverse tubules and stimulate DuRAl the release of Ca++ from the sarcoplasmic reticulum into the cytoplasm. Ca* diffuses toward the myofibrils and causes contraction Nucleus Transverse tubule(T tubules Mitochondrion 1008 Part XIlI Animal Form and Function
The Control of Muscle Contraction The Role of Ca++ in Contraction When a muscle is relaxed, its myosin heads are “cocked” and ready, through the splitting of ATP, but are unable to bind to actin. This is because the attachment sites for the myosin heads on the actin are physically blocked by another protein, known as tropomyosin, in the thin filaments. Cross-bridges therefore cannot form in the relaxed muscle, and the filaments cannot slide. In order to contract a muscle, the tropomyosin must be moved out of the way so that the myosin heads can bind to actin. This requires the function of troponin, a regulatory protein that binds to the tropomyosin. The troponin and tropomyosin form a complex that is regulated by the calcium ion (Ca++) concentration of the muscle cell cytoplasm. When the Ca++ concentration of the muscle cell cytoplasm is low, tropomyosin inhibits cross-bridge formation and the muscle is relaxed (figure 50.14). When the Ca++ concentration is raised, Ca++ binds to troponin. This causes the troponin-tropomyosin complex to be shifted away from the attachment sites for the myosin heads on the actin. Cross-bridges can thus form, undergo power strokes, and produce muscle contraction. Where does the Ca++ come from? Muscle fibers store Ca++ in a modified endoplasmic reticulum called a sarcoplasmic reticulum, or SR (figure 50.15). When a muscle fiber is stimulated to contract, an electrical impulse travels into the muscle fiber down invaginations called the transverse tubules (T tubules). This triggers the release of Ca++ from the SR. Ca++ then diffuses into the myofibrils, where it binds to troponin and causes contraction. The contraction of muscles is regulated by nerve activity, and so nerves must influence the distribution of Ca++ in the muscle fiber. 1008 Part XIII Animal Form and Function Myosin head Myosin Troponin Tropomyosin Binding sites for cross-bridges blocked Binding sites for cross-bridges exposed Actin (a) (b) Ca++ Ca++ Ca++ Ca++ FIGURE 50.14 How calcium controls striated muscle contraction. (a) When the muscle is at rest, a long filament of the protein tropomyosin blocks the myosin-binding sites on the actin molecule. Because myosin is unable to form cross-bridges with actin at these sites, muscle contraction cannot occur. (b) When Ca++ binds to another protein, troponin, the Ca++-troponin complex displaces tropomyosin and exposes the myosin-binding sites on actin, permitting cross-bridges to form and contraction to occur. Nucleus Mitochondrion Myofibril Sarcolemma Z line Sarcoplasmic reticulum Transverse tubule (T tubules) FIGURE 50.15 The relationship between the myofibrils, transverse tubules, and sarcoplasmic reticulum. Impulses travel down the axon of a motor neuron that synapses with a muscle fiber. The impulses are conducted along the transverse tubules and stimulate the release of Ca++ from the sarcoplasmic reticulum into the cytoplasm. Ca++ diffuses toward the myofibrils and causes contraction
Nerves stimulate Contraction Muscles are stimulated to contract by motor neurons. The particular motor neurons that stimulate skeletal muscles, as posed to cardiac and smooth muscles, are called somatic motor neurons. The axon(see figure 49. 12)of a somatic motor neuron extends from the neuron cell body and Motor unit branches to make functional connections, or synapses, with a number of muscle fibers. (Synapses are discussed in more detail in chapter 54. )One axon can stimulate many muscle fibers, and in some animals a muscle fiber may be inner vated by more than one motor neuron. However, in hu- mans each muscle fiber only has a single synapse with a branch of one axon When a somatic motor neuron produces electrochemi- impulses, it stimulates contraction of the muscle fibers it innervates(makes synapses with) through the following 1. The motor neuron, at its synapse with the muscle fibers. releases a chemical known as a neurotransmit- (a)Tapping toe (b)Running matic motor neurons is acetylcholine(ACh). ACh FIGURE 50.16 acts on the muscle fiber membrane to stimulate the The number and size of motor units. (a)Weak, precise muscle er an muscle fiber to produce its own stronger movements require additional motor units that are 2. The impulses spread along the membrane of the muscle fiber and are carried into the muscle fibers through the t tubules for coordinated movements of the skeleton Muscles that 3. The T tubules conduct the impulses toward the sar- require a finer degree of control have smaller motor units coplasmic reticulum, which then release Cat+t. As de-(fewer muscle fibers per neuron) than muscles that re- scribed earlier, the Ca+ binds to troponin, which ex- quire less precise control but must exert more force. For poses the cross-bridge binding sites on the actin xample, there are only a few muscle fibers per motor myofilaments, stimulating muscle contraction neuron in the muscles that move the eyes, while there are several hundred per motor neuron in the large muscles of When impulses from the nerve stop, the nerve stops re- the legs leasing ACh. This stops the production of impulses in the Most muscles contain motor units in a variety of sizes muscle fiber. When the T tubules no longer produce which can be selectively activated by the nervous system. pulses, Cat+ is brought back into the SR by active trans- The weakest contractions of a muscle involve the activa port. Troponin is no longer bound to Ca**, so tropomyosin tion of a few small motor units. If a slightly stronger con returns to its inhibitory position, allowing the muscle to traction is necessary, additional small motor units are also activated. The initial increments to the total force gener The involvement of Ca++ in muscle contraction is called, ated by the muscle are therefore relatively small. As ever excitation-contraction coupling because it is the releas greater forces are required, more and lar rger motor units of Ca++ that links the excitation of the muscle fiber by the are brought into action, and the force increments become motor neuron to the contraction of the muscle larger. The nervous systems use of increased numbers and sizes of motor units to produce a stronger contraction is Motor Units and recruitment termed recruitment e muscle fiber responds in an all-or-none fashi The cross-bridges are prevented from binding to actin to stimulation. The response of an entire muscle depend by tropomyosin in a relaxed muscle. In order for a upon the number of individual fibers involved. The set of muscle to contract. Ca++ must be released from the muscle fibers innervated by all axonal branches of a given sarcoplasmic reticulum, where it is stored, so that it can motor neuron is defined as a motor unit(figure 50.16 bind to troponin and cause the tropomyosin to shift its Every time the motor neuron produces impulses, all mus- position in the thin filaments. Muscle contraction is cle fibers in that motor unit contract together. The divi- stimulated by neurons. Varying sizes and numbers of sion of the muscle into motor units allows the muscles motor units are used to produce different types of strength of contraction to be finely graded, a requirement Chapter 50 Locomotion 1009
Nerves Stimulate Contraction Muscles are stimulated to contract by motor neurons. The particular motor neurons that stimulate skeletal muscles, as opposed to cardiac and smooth muscles, are called somatic motor neurons. The axon (see figure 49.12) of a somatic motor neuron extends from the neuron cell body and branches to make functional connections, or synapses, with a number of muscle fibers. (Synapses are discussed in more detail in chapter 54.) One axon can stimulate many muscle fibers, and in some animals a muscle fiber may be innervated by more than one motor neuron. However, in humans each muscle fiber only has a single synapse with a branch of one axon. When a somatic motor neuron produces electrochemical impulses, it stimulates contraction of the muscle fibers it innervates (makes synapses with) through the following events: 1. The motor neuron, at its synapse with the muscle fibers, releases a chemical known as a neurotransmitter. The specific neurotransmitter released by somatic motor neurons is acetylcholine (ACh). ACh acts on the muscle fiber membrane to stimulate the muscle fiber to produce its own electrochemical impulses. 2. The impulses spread along the membrane of the muscle fiber and are carried into the muscle fibers through the T tubules. 3. The T tubules conduct the impulses toward the sarcoplasmic reticulum, which then release Ca++. As described earlier, the Ca++ binds to troponin, which exposes the cross-bridge binding sites on the actin myofilaments, stimulating muscle contraction. When impulses from the nerve stop, the nerve stops releasing ACh. This stops the production of impulses in the muscle fiber. When the T tubules no longer produce impulses, Ca++ is brought back into the SR by active transport. Troponin is no longer bound to Ca++, so tropomyosin returns to its inhibitory position, allowing the muscle to relax. The involvement of Ca++ in muscle contraction is called, excitation-contraction coupling because it is the release of Ca++ that links the excitation of the muscle fiber by the motor neuron to the contraction of the muscle. Motor Units and Recruitment A single muscle fiber responds in an all-or-none fashion to stimulation. The response of an entire muscle depends upon the number of individual fibers involved. The set of muscle fibers innervated by all axonal branches of a given motor neuron is defined as a motor unit (figure 50.16). Every time the motor neuron produces impulses, all muscle fibers in that motor unit contract together. The division of the muscle into motor units allows the muscle’s strength of contraction to be finely graded, a requirement for coordinated movements of the skeleton. Muscles that require a finer degree of control have smaller motor units (fewer muscle fibers per neuron) than muscles that require less precise control but must exert more force. For example, there are only a few muscle fibers per motor neuron in the muscles that move the eyes, while there are several hundred per motor neuron in the large muscles of the legs. Most muscles contain motor units in a variety of sizes, which can be selectively activated by the nervous system. The weakest contractions of a muscle involve the activation of a few small motor units. If a slightly stronger contraction is necessary, additional small motor units are also activated. The initial increments to the total force generated by the muscle are therefore relatively small. As ever greater forces are required, more and larger motor units are brought into action, and the force increments become larger. The nervous system’s use of increased numbers and sizes of motor units to produce a stronger contraction is termed recruitment. The cross-bridges are prevented from binding to actin by tropomyosin in a relaxed muscle. In order for a muscle to contract, Ca++ must be released from the sarcoplasmic reticulum, where it is stored, so that it can bind to troponin and cause the tropomyosin to shift its position in the thin filaments. Muscle contraction is stimulated by neurons. Varying sizes and numbers of motor units are used to produce different types of muscle contractions. Chapter 50 Locomotion 1009 Muscle fiber Motor unit (a) Tapping toe (b) Running FIGURE 50.16 The number and size of motor units. (a) Weak, precise muscle contractions use smaller and fewer motor units. (b) Larger and stronger movements require additional motor units that are larger
Types of Muscle Fibers Muscles like the soleus must be able to sustain a con- action for a long period of time without fat Muscle fiber Twitches resistance to fatigue demonstrated by these muscles is An isolated skeletal muscle can be studied by stimulating it aided by other characteristics of slow-twitch(type D) artificially with electric shocks. If a muscle is stimulated fibers that endow them with a high capacity for aerobic with a single electric shock, it will quickly contract and respiration. Slow-twitch fibers have a rich capillary sup- relax in a response called a twitch. Increasing the stimulus ply, numerous mitochondria and aerobic respiratory en- roltage increases the strength of the twitch up to a maxi- zymes, and a high concentration of myoglobin pigment. mum. If a second electric shock is delivered immediately Myoglobin is a red pigment, similar to the hemoglobin in fter the first, it will produce a second twitch that may p, Becaes the delivery of oxygen to the slow-twitch fibers sponse is called summation(figure 50.17) If the stimulator is set to deliver an increasing frequency fibers are also called red fibers of electric shocks automatically, the relaxation time be- The thicker, fast-twitch(type If)fibers have fewer aries and mitochondria than slow-twitch fibers and not as tween successive twitches will get shorter and shorter, as much myoglobin; hence, these fibers are also called wbite the strength of contraction increases. Finally, at a particular of stimulation there is no visible relaxation be- fibers. Fast-twitch fibers are adapted to respire anaerobi tween successive twitches Contraction is smooth and sus- cally by using a large store of glycogen and high concentra- ed, as it is during normal muscle contraction in the tions of glycolytic enzymes. Fast-twitch fibers are adapted for the rapid generation of power and can grow thi Cker an term tetanus should not be confused with the disease stronger in response to weight training. The"dark meat Skeletal muscle fibers can be divided on the basis of respective muscles with primarily red and white fibers of muscle contracture, or tetany. heir contraction speed into slow-twitch, or type I In addition to the type I(slow-twitch) and type II(fast ibers, and fast-twitch, or type Il, fibers. The muscles twitch) fibers, human muscles also have an intermediate that move the eyes, for example, have a high proportion form of fibers that are fast-twitch but also have a high ox- of fast-twitch fibers and reach maximum tension in about idative capacity, and so are more resistant to fatigue. En- 7.3 milliseconds; the soleus muscle in the leg, by con durance training increases the proportion of these fibers in ast, has a high proportion of slow-twitch fibers and re muscles quires about 100 milliseconds to reach maximum tension (figure 50.18). etanus Incomplete Twitches Stimul↑ ↑↑↑个↑↑↑↑ Time FIGURE 50.17 Muscle twitches summate to produce a sustained, tetanized contraction. This pattern is produced when the muscle is stimul rically or naturally by neurons. Tetanus, a smooth, sustained contraction, is the normal type of muscle contraction in the body 1010 Part XIlI Animal Form and Function
Types of Muscle Fibers Muscle Fiber Twitches An isolated skeletal muscle can be studied by stimulating it artificially with electric shocks. If a muscle is stimulated with a single electric shock, it will quickly contract and relax in a response called a twitch. Increasing the stimulus voltage increases the strength of the twitch up to a maximum. If a second electric shock is delivered immediately after the first, it will produce a second twitch that may partially “ride piggyback” on the first. This cumulative response is called summation (figure 50.17). If the stimulator is set to deliver an increasing frequency of electric shocks automatically, the relaxation time between successive twitches will get shorter and shorter, as the strength of contraction increases. Finally, at a particular frequency of stimulation, there is no visible relaxation between successive twitches. Contraction is smooth and sustained, as it is during normal muscle contraction in the body. This smooth, sustained contraction is called tetanus. (The term tetanus should not be confused with the disease of the same name, which is accompanied by a painful state of muscle contracture, or tetany.) Skeletal muscle fibers can be divided on the basis of their contraction speed into slow-twitch, or type I, fibers, and fast-twitch, or type II, fibers. The muscles that move the eyes, for example, have a high proportion of fast-twitch fibers and reach maximum tension in about 7.3 milliseconds; the soleus muscle in the leg, by contrast, has a high proportion of slow-twitch fibers and requires about 100 milliseconds to reach maximum tension (figure 50.18). Muscles like the soleus must be able to sustain a contraction for a long period of time without fatigue. The resistance to fatigue demonstrated by these muscles is aided by other characteristics of slow-twitch (type I) fibers that endow them with a high capacity for aerobic respiration. Slow-twitch fibers have a rich capillary supply, numerous mitochondria and aerobic respiratory enzymes, and a high concentration of myoglobin pigment. Myoglobin is a red pigment, similar to the hemoglobin in red blood cells, but its higher affinity for oxygen improves the delivery of oxygen to the slow-twitch fibers. Because of their high myoglobin content, slow-twitch fibers are also called red fibers. The thicker, fast-twitch (type II) fibers have fewer capillaries and mitochondria than slow-twitch fibers and not as much myoglobin; hence, these fibers are also called white fibers. Fast-twitch fibers are adapted to respire anaerobically by using a large store of glycogen and high concentrations of glycolytic enzymes. Fast-twitch fibers are adapted for the rapid generation of power and can grow thicker and stronger in response to weight training. The “dark meat” and “white meat” found in meat such as chicken and turkey consists of muscles with primarily red and white fibers, respectively. In addition to the type I (slow-twitch) and type II (fasttwitch) fibers, human muscles also have an intermediate form of fibers that are fast-twitch but also have a high oxidative capacity, and so are more resistant to fatigue. Endurance training increases the proportion of these fibers in muscles. 1010 Part XIII Animal Form and Function Twitches Incomplete tetanus • • • • • • Complete tetanus Summation Amplitude of muscle contractions Stimuli Time FIGURE 50.17 Muscle twitches summate to produce a sustained, tetanized contraction. This pattern is produced when the muscle is stimulated electrically or naturally by neurons. Tetanus, a smooth, sustained contraction, is the normal type of muscle contraction in the body