14 USMLE Road Map: Physiology A band I band hin filaments Thick filaments Figure 1-5. Sarcomere structure the a bands co tain the thick filaments the i bands contain the thin Z line. The Z line maintains the regular spacing of the chin filaments within the sarcomere. The space be tween terminations of thin filaments is called the h zone, and the denser area within the h zone is termed the m line e. Tropomyosin is an elongated protein that lies within the two grooves formed by the double stranded F-actin( Figure 1-6) E. Each thin filament contains 40-60 tropomyosin molecules T olex of three separate pro (1)Troponin T binds the other two troponin subunits to tropomyosin (2) Troponin C binds Ca2*, the crucial regulatory step in muscle contrac ()Troponin I is responsible for the inhibitory conformation of the tropomyosin-troponin complex observed in the absence of Ca 3. Tubules, a tubular network, are located at the junctions of A bands and I bands and contain a protein called the dihydropyridine recep tor. 4. The sarcoplasmic reticulum(SR)is the site of Ca storage near the trans- verse tubules (T-tubules). It contains a Ca-release channel known as the ryanodine receptor E. Several steps are involved in the mechanics of muscle contraction 1. Action potentials in muscle cell membrane cause depolarization of the T-tubules, which opens Ca-release channels in the SR and increases intracel- lular Ca2 2. Ca'releases the troponin-tropomyosin inhibitory influence so that the active sites on each G-actin monomer are uncovered
14 USMLE Road Map: Physiology N H zone M line I band A band Thin filaments Thick filaments I band Z line Cross section e. Tropomyosin is an elongated protein that lies within the two grooves formed by the double stranded F-actin (Figure 1–6). f. Each thin filament contains 40–60 tropomyosin molecules. g. Troponin is a complex of three separate proteins: (1) Troponin T binds the other two troponin subunits to tropomyosin. (2) Troponin C binds Ca2+, the crucial regulatory step in muscle contraction. (3) Troponin I is responsible for the inhibitory conformation of the tropomyosin-troponin complex observed in the absence of Ca2+. 3. Tubules, a tubular network, are located at the junctions of A bands and I bands and contain a protein called the dihydropyridine receptor. 4. The sarcoplasmic reticulum (SR) is the site of Ca2+ storage near the transverse tubules (T-tubules). It contains a Ca2+-release channel known as the ryanodine receptor. E. Several steps are involved in the mechanics of muscle contraction: 1. Action potentials in muscle cell membrane cause depolarization of the T-tubules, which opens Ca2+-release channels in the SR and increases intracellular Ca2+. 2. Ca2+ releases the troponin-tropomyosin inhibitory influence so that the active sites on each G-actin monomer are uncovered. Figure 1–5. Sarcomere structure. The A bands contain the thick filaments. The I bands contain the thin filaments, which are attached to and extend from the Z line. The Z line maintains the regular spacing of the thin filaments within the sarcomere. The space between terminations of thin filaments is called the H zone, and the denser area within the H zone is termed the M line. 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 14
Chapter 1: Cell Physiology 15 Actin filament Tropomyosin Troponin binding site Active site Actin Head ATP- Myosin filament Figure 1-6. Thin filament structure. 3. The myosin globular heads that protrude from the thick filament bind with 4. Intramolecular forces(stored energy) within the myosin molecules allow myosin to flex in the so-called hinge regions. These areas are the two pro- teolytic enzyme-sensitive regions in the myosin molecule. The action of flex ing of the myosin molecule causes the globular heads(still attached to actin) to tilt toward the center of the sarcomere. This movement, called the power stroke, creates tension that results from shortening of individual sarcomeres 5. Immediately after the tilt, the crossbridge is broken and the globular heads snap back to the upright position. 6. At this point, a new crossbridge can be formed if ATP and Ca *are available in the vicinity of thick and thin filaments In the absence of Ca, crossbridge formation is not possible. 7. Relaxation occurs when Ca*uptake into the SR lowers intracellular Ca". F. The biochemical events that occur during a muscle contraction cycle involve an active complex and the rigor complex. 1. Myosin with ATP bound to it(myosin-ATP complex)has a low affinity for tropomyosin rotates out of the way so that the active sites on G=opomyosin, the G-actin active sites. When Ca binds to troponin and tro covered. Myosin-AtP is simultaneously hydrolyzed to myosin-ADP, which has a high affinity for the g-actin active sites. Consequently, an active com- lex, or crossbridge, is formed between actin and myosin-ADP 2. ADP is released from myosin, and the globular heads tilt toward the center of the sarcomere, producing tension. At this stage, the rigor complex is formed between actin and myosin. 3. ATP then binds to myosin, and the myosin-ATP complex breaks the cross- bridge and the globular heads snap back to the upright position 4. The cycle is ready to start again in the presence of Cal
Chapter 1: Cell Physiology 15 N Actin filament Calcium– Tropomyosin Troponin binding site Active site Actin Myosin filament Heavy meromyosin Tail Head Actin– binding site ATP– binding site Light meromyosin Figure 1–6. Thin filament structure. 3. The myosin globular heads that protrude from the thick filament bind with G-actin active sites, thus forming crossbridges. 4. Intramolecular forces (stored energy) within the myosin molecules allow myosin to flex in the so-called hinge regions. These areas are the two proteolytic enzyme–sensitive regions in the myosin molecule. The action of flexing of the myosin molecule causes the globular heads (still attached to actin) to tilt toward the center of the sarcomere. This movement, called the power stroke, creates tension that results from shortening of individual sarcomeres. 5. Immediately after the tilt, the crossbridge is broken and the globular heads snap back to the upright position. 6. At this point, a new crossbridge can be formed if ATP and Ca2+ are available in the vicinity of thick and thin filaments. In the absence of Ca2+, crossbridge formation is not possible. 7. Relaxation occurs when Ca2+ uptake into the SR lowers intracellular Ca2+. F. The biochemical events that occur during a muscle contraction cycle involve an active complex and the rigor complex. 1. Myosin with ATP bound to it (myosin-ATP complex) has a low affinity for the G-actin active sites. When Ca2+ binds to troponin and tropomyosin, tropomyosin rotates out of the way so that the active sites on G-actin are uncovered. Myosin-ATP is simultaneously hydrolyzed to myosin-ADP, which has a high affinity for the G-actin active sites. Consequently, an active complex, or crossbridge, is formed between actin and myosin-ADP. 2. ADP is released from myosin, and the globular heads tilt toward the center of the sarcomere, producing tension. At this stage, the rigor complex is formed between actin and myosin. 3. ATP then binds to myosin, and the myosin-ATP complex breaks the crossbridge and the globular heads snap back to the upright position. 4. The cycle is ready to start again in the presence of Ca2+. 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 15
16 USMLE Road Map: Physiology G. Skeletal muscle enters a state of prolonged stiffness termed rigor mortis at death 1. Rigor mortis occurs because, with death, muscle cells are no longer able to synthesize ATP. 2. In the absence of ATP, the crossbridges between myosin and actin are unable to dissociate 3. After 15-25 hours, proteolytic enzymes released from lysosomes begin to break down actin and myosin. H. Practical aspects of filament interactions involve the relationship between muscle length and tension. 1. In an isometric contraction, the muscle length is held constant during the development of force. An example would be an individual pushing against an immovable object such as the wall of a house 2. In an isotonic contraction, the muscle shortens while exerting a constant force. An example would be an individual lifting a glass of water to his or her mouth 3. The tension that a stimulated muscle develops when it contracts isometrical (total tension) and the passive tension exerted by the unstimulated muscle vary with the length of the muscle fiber. The difference between the two val- ues is the duced by the contractile process, the active tension(fig- 1-7) 4. The amount of active tension developed with a contraction decreases from its maximum as the muscle is either shortened or lengthened prior to the contrac- tile stimulus Active tension = Passive tension Stimulat 品 e 1-7. The length-tension relationship is the relationship between the and the amount tension on the mus- refers to the tensi contractile forces he muscle is stim force acting on the muscle when the Total tension on the muscle is the sum of the active and passive tensions
16 USMLE Road Map: Physiology N 0.5X 1X 2X Sarcomere length (X=~2.0µ) Muscle tension Adjust muscle length Stimulate Measure tension Active tension Passive tension Total tension 0 1 2 3 4 1 2 3 Figure 1–7. The length-tension relationship is the relationship between the length of the muscle and the amount of active or passive tension on the muscle. Active tension refers to the tension generated by the contractile forces when the muscle is stimulated, whereas passive tension refers to the elastic force acting on the muscle when the muscle is stretched. Total tension on the muscle is the sum of the active and passive tensions. G. Skeletal muscle enters a state of prolonged stiffness termed rigor mortis at death. 1. Rigor mortis occurs because, with death, muscle cells are no longer able to synthesize ATP. 2. In the absence of ATP, the crossbridges between myosin and actin are unable to dissociate. 3. After 15–25 hours, proteolytic enzymes released from lysosomes begin to break down actin and myosin. H. Practical aspects of filament interactions involve the relationship between muscle length and tension. 1. In an isometric contraction, the muscle length is held constant during the development of force. An example would be an individual pushing against an immovable object such as the wall of a house. 2. In an isotonic contraction, the muscle shortens while exerting a constant force. An example would be an individual lifting a glass of water to his or her mouth. 3. The tension that a stimulated muscle develops when it contracts isometrically (total tension) and the passive tension exerted by the unstimulated muscle vary with the length of the muscle fiber. The difference between the two values is the tension produced by the contractile process, the active tension (Figure 1–7). 4. The amount of active tension developed with a contraction decreases from its maximum as the muscle is either shortened or lengthened prior to the contractile stimulus. 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 16
Chapter 1: Cell Physiology 17 5. Active tension developed is proportional to the number of crossbridges formed 6. Tension is reduced when the sarcomere is shortened to a point where thin fila- ments overlap and prevent one another from for 7. Thus, isometric tension produced depends on the degree of overlap of the thick and thin filaments, which dictates the number of crossbridges that can be formed L. The force-velocity relationship refers to the relationship between the load(or weight) placed on a muscle and the velocity at which that muscle contracts while lifting the load 1. Velocity is the distance an object moves per unit time. a load can be thought of as a weight that the muscle is attempting to move via an isotonic contrac- tion, for example, when a weightlifter tries to lift a series of progressively heav- 2. A muscle can contract most rapidly with no load. As loads increase, however, the velocity at which the muscle lifts the weight decreases 3. When the weight equals the maximum amount of force that the muscle can generate, the velocity becomes zero. In this case the contraction becomes iso- metric(eg, the muscle contracts but does not shorten) J. The functional unit of a muscle is called a motor unit. 1. A motor unit consists of one motor neuron its axon, and all the muscle cells innervated by that motor neuron In adults, each muscle fiber is innervated by a single motor axon. 2. In general, motor units in small muscles that react to stimulation rapidly and subserve functions that require fine control have a low number of muscle fibers. An example is laryngeal muscle, in which a motor unit has approxi- mately 2-3 muscle fibers per motor neuron 3. Motor units in large muscles that subserve functions not requiring fine motor control tend to have a larger number of muscle fibers. An example is the gastrocnemius, in which a motor unit contains approximately 500 muscle 4. Because all the muscle cells in a motor unit contract together, the fundamental unit of contraction of a whole muscle is the contraction produced by a motor 5. Increased tension development in skeletal muscle is attained by a. Wave summation(eg, increasing stimulus frequency of a single motor neuro b. Summation, or recruitment, of motor units. Besides increasing tension de elopment, recruitment allows a movement to be continuous and smooth because different motor units fire asynchronously; that is, motor unit is contracting, another might be at rest K. a contraction can be a single, brief contraction or a maintained contraction due o continuous excitation of muscle fibers 1. A single contractile event(eg, twitch) is initiated by a single action potential from a motor neuron reaching the neuromuscular junction 2. If a second stimulus is applied before the muscle fibers in the motor unit have relaxed the second contractile event builds on the first. it can be said that the two contractions summate
Chapter 1: Cell Physiology 17 N 5. Active tension developed is proportional to the number of crossbridges formed. 6. Tension is reduced when the sarcomere is shortened to a point where thin filaments overlap and prevent one another from forming crossbridges with myosin. 7. Thus, isometric tension produced depends on the degree of overlap of the thick and thin filaments, which dictates the number of crossbridges that can be formed. I. The force-velocity relationship refers to the relationship between the load (or weight) placed on a muscle and the velocity at which that muscle contracts while lifting the load. 1. Velocity is the distance an object moves per unit time. A load can be thought of as a weight that the muscle is attempting to move via an isotonic contraction, for example, when a weightlifter tries to lift a series of progressively heavier weights. 2. A muscle can contract most rapidly with no load. As loads increase, however, the velocity at which the muscle lifts the weight decreases. 3. When the weight equals the maximum amount of force that the muscle can generate, the velocity becomes zero. In this case the contraction becomes isometric (eg, the muscle contracts but does not shorten). J. The functional unit of a muscle is called a motor unit. 1. A motor unit consists of one motor neuron, its axon, and all the muscle cells innervated by that motor neuron. In adults, each muscle fiber is innervated by a single motor axon. 2. In general, motor units in small muscles that react to stimulation rapidly and subserve functions that require fine control have a low number of muscle fibers. An example is laryngeal muscle, in which a motor unit has approximately 2–3 muscle fibers per motor neuron. 3. Motor units in large muscles that subserve functions not requiring fine motor control tend to have a larger number of muscle fibers. An example is the gastrocnemius, in which a motor unit contains approximately 500 muscle fibers per motor neuron. 4. Because all the muscle cells in a motor unit contract together, the fundamental unit of contraction of a whole muscle is the contraction produced by a motor unit. 5. Increased tension development in skeletal muscle is attained by a. Wave summation (eg, increasing stimulus frequency of a single motor neuron). b. Summation, or recruitment, of motor units. Besides increasing tension development, recruitment allows a movement to be continuous and smooth because different motor units fire asynchronously; that is, while one motor unit is contracting, another might be at rest. K. A contraction can be a single, brief contraction or a maintained contraction due to continuous excitation of muscle fibers. 1. A single contractile event (eg, twitch) is initiated by a single action potential from a motor neuron reaching the neuromuscular junction. 2. If a second stimulus is applied before the muscle fibers in the motor unit have relaxed, the second contractile event builds on the first. It can be said that the two contractions summate. 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 17
18 USMLE Road Map: Physiology a. This summation of contractions occurs when stimulation frequencies reach about 10 per second. As the frequency of stimulation is increased, the developed force continues to sum until a maximum developed force is b. At this point, the individual contraction-relaxation cycles fuse to produce a single smooth curve called tetanus(Figure 1-8). Tetanus occurs in skeletal muscle because the refractory period(ie, the time during which the tissue does not respond to a second stimulus) is short relative to the contraction V. Neuromuscular and Synaptic Transmission A. The activity of various skeletal muscle groups is controlled by the central ne ous system through innervation of individual muscle fibers B. Each motor nerve sends processes to each muscle fiber in the motor unit. C. Where a motor nerve comes in contact with the surface of a muscle fiber, a highly organized and specialized structure is formed known as a neuromuscular junction,or motor endplate( Figure 1-9) D. The invagination of the muscle fiber sarcolemma forms the synaptic trough. E. The space between the axon terminal and invaginated sarcolemma is called the haptic cleft F. Schwann cells are usually seen in the vicinity of the motor endplate and may iso late the synaptic cleft from extracellular space G. The neurotransmitter acetylcholine is stored in synaptic vesicles located in the H. The biosynthesis of acetylcholine involves the reaction of choline with active acetate(acetyl-CoA) Tetanus Contractile force Stimulus Figure 1-8. Recordings of contractile force during twitch con- tractions(left)and tetanic contraction(right) of skeletal muscle. A twitch contraction is a single brief muscle contraction that oc- urs in response to a single threshold stimulus. Tetanic tion or tetanus, is a constant contraction of skeletal muscle due to continuous excitation of muscle fibers
18 USMLE Road Map: Physiology N Tetanus Contractile force Stimulus Figure 1–8. Recordings of contractile force during twitch contractions (left) and tetanic contraction (right) of skeletal muscle. A twitch contraction is a single brief muscle contraction that occurs in response to a single threshold stimulus. Tetanic contraction, or tetanus, is a constant contraction of skeletal muscle due to continuous excitation of muscle fibers. a. This summation of contractions occurs when stimulation frequencies reach about 10 per second. As the frequency of stimulation is increased, the developed force continues to sum until a maximum developed force is reached. b. At this point, the individual contraction-relaxation cycles fuse to produce a single smooth curve called tetanus (Figure 1–8). Tetanus occurs in skeletal muscle because the refractory period (ie, the time during which the tissue does not respond to a second stimulus) is short relative to the contraction time. VI. Neuromuscular and Synaptic Transmission A. The activity of various skeletal muscle groups is controlled by the central nervous system through innervation of individual muscle fibers. B. Each motor nerve sends processes to each muscle fiber in the motor unit. C. Where a motor nerve comes in contact with the surface of a muscle fiber, a highly organized and specialized structure is formed known as a neuromuscular junction, or motor endplate (Figure 1–9). D. The invagination of the muscle fiber sarcolemma forms the synaptic trough. E. The space between the axon terminal and invaginated sarcolemma is called the synaptic cleft. F. Schwann cells are usually seen in the vicinity of the motor endplate and may isolate the synaptic cleft from extracellular space. G. The neurotransmitter acetylcholine is stored in synaptic vesicles located in the axon terminal. H. The biosynthesis of acetylcholine involves the reaction of choline with active acetate (acetyl-CoA). 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 18