Muscles and Contraction

Transcription

1 Muscles and Contraction Muscle tissue forms the organs called muscle. Three types of muscle tissue are (1) skeletal, (2) cardiac, and (3) smooth. Anatomy and Physiology Text and Laboratory Workbook, Stephen G. Davenport, Copyright 2006, All Rights Reserved, no part of this publication can be used for any commercial purpose. Permission requests should be addressed to Stephen G. Davenport, Link Publishing, P.O. Box 15562, San Antonio, TX, Types and Functions of Muscle Tissue Skeletal Muscle Tissue Skeletal muscle tissue forms the skeletal muscles. Skeletal muscles are associated with the skeleton and function in: Producing body movements. Body movements are produced when skeletal muscles manipulate the body s skeleton allowing movements such as walking, running, and the movement of a variety of objects. Maintenance of posture. Skeletal muscles provide for the continuous maintenance of body position. Body positions such as sitting, standing, leaning, etc. require the contraction of skeletal muscles. Generation of heat. Skeletal muscle contraction produces most of the body s heat. Mechanisms for heat removal (such as sweating) and heat generation (such as shivering) function in the maintenance of body temperature. Types and Functions of Muscle Tissue Cardiac Muscle Tissue Cardiac muscle tissue forms the muscle of the heart. Cardiac muscle functions in: Producing blood flow through the chambers of the heart. The heart is a four-chamber pump. Its two superior chambers, the atria, help push blood into the lower two chambers, the ventricles. The ventricles push blood and generate the blood pressures that drive the blood into two primary circuits. Producing blood flow and pressure for two primary circuits: (1) pulmonary circuit, and (2) systemic circuit. The pulmonary circuit involves blood flow through the lungs for gas exchange. In this circuit blood loses carbon dioxide and becomes rich in oxygen. The systemic circuit involves blood flow throughout the body. In this circuit blood delivers its vital cargo of oxygen, nutrients, hormones, etc. to the body s cells and removes waste products. Types and Functions of Muscle Tissue Smooth Muscle Tissue Smooth muscle tissue mostly forms the muscular portion of the walls of most of the body s hollow organs, especially of the digestive, respiratory, urinary, and reproductive tracts. Smooth muscle functions include: Regulating the diameter of hollow organs. This function is especially seen in the small arterial blood vessels called arterioles. Regulation of the diameter of small arteries called arterioles has a major impact on blood flow and blood pressure. Regulation of movement of materials through hollow organs. This function is especially seen in the digestive tract. Contraction of smooth muscle propels and mixes the contents of most of the digestive tract, especially of the stomach, small intestine, and large intestine. Characteristics of Muscle Tissue Characteristics of Muscle Tissue All three types of muscle tissue share the characteristics of: (1) excitability, (2) contractility, (3) extensibility, and (4) elasticity. Additionally, muscle tissues protect and contribute to the framework (structure) of their associated organs. Muscles protect their internal organs, such as blood vessels and nerves, by functioning as a cushion. Additionally, skeletal muscles protects the body s internal organs, especially those of the abdominal region. Excitability Excitability, or irritability, refers to the ability of the muscle fiber to be activated by and to react to a stimulus. A stimulus is something that rouses or incites to activity. Muscle tissue may be stimulated by chemicals such as neurotransmitters and hormones or electrical stimuli such as action potentials produced by the local movement of electrolytes. Excitation of the fiber leads to the contraction of the fiber. Contractility Contractility is the ability of muscle fibers to draw together, or shorten. In this process muscle fibers produce tension (a tightening), which is the force of the contraction. 1

2 Characteristics of Muscle Tissue Skeletal Muscles Anatomy of a Skeletal Muscle Extensibility Extensibility is the ability of muscle fibers to elongate, or stretch. The extensibility of muscles is especially apparent in skeletal muscle flexion and extension. As one muscle contracts and the angle at the joint decreases (flexion), an opposing muscle is extended, or stretched. Extensibility is also apparent in the smooth muscle of the stomach, allowing filling of the stomach as the muscle stretches. Elasticity Elasticity is the ability of the muscle fibers to return to its normal resting length after contraction or extension. Elasticity allows muscle fibers to return their optimal working length. Anatomy of a Skeletal Muscle Anatomy of a Skeletal Muscle Skeletal muscles are formed from muscle skeletal muscle fibers (cells) and their associated connective tissues. The number of fibers and the amount of connective tissues in a muscle varies from muscle to muscle. A muscle is well supplied with blood vessels and nerves. Blood vessels are essential for the delivery of nutrients, oxygen, etc. and for the removal of waste materials. Nerves associated with muscles typically have both sensory and motor functions. Sensory endings (receptors) are found within the muscle (muscle spindles) and in the muscle s connective tissues. Additional receptors are found within tendons and the connective tissues of the joints. Sensory receptors monitor a muscle s contraction and initiate nerve impulses that are conducted along sensory fibers (axons) to the central nervous system for integration. Motor fibers (axons) originate from motor neurons in the central nervous system and terminate on muscle fibers at neuromuscular junctions. Motor fibers conduct action potentials (nerve impulses) to the muscle fiber. Acetylcholine (a neurotransmitter) released at the neuromuscular junctions supplies the stimulus which initiates excitation of the skeletal muscle fiber. Skeletal Muscle Fiber The functional unit of a skeletal muscle is the muscle fiber. An individual fiber is long, cylindrical, multinucleate, striated, and typically lies parallel to adjacent fibers. Each individual fiber has at least one connection (synapse) with a motor neuron at a nerve-muscle site called a neuromuscular junction. Each fiber is surrounded by a connective tissue sheath called the endomysium. Fibers and their associated sheaths of endomysium are arranged in groups and surround by connective tissue, the perimysium, to form fascicles. Figure 16.1 The anatomy of a typical skeletal muscle. The functional unit of a muscle is the muscle fiber (cell). 2

3 Connective Tissues of a Muscle Connective Tissues of a Muscle Endomysium Each muscle fiber is surrounded by and attached to a connective tissue covering called the endomysium. The endomysium consists of short branching reticular fibers, fibroblasts, and matrix. As the muscle fiber contracts, force is transferred to the endomysium. The endomysium connects and transfers force to its associated perimysium. Perimysium The perimysium is a layer of fibrous connective tissue that is continuous with the endomysium and surrounds a group of muscle fibers, a fascicle. The perimysium of the fascicles is continuous with the outer layer of the muscle, the epimysium Connective Tissues of a Muscle Epimysium The epimysium is the outer layer of dense irregular fibrous connective tissue that surrounds the entire muscle. The epimysium is continuous with the perimysium and in most muscles continues as dense regular connective tissue to form a tendon. Tendons connect muscles to bones. A tendon connects to the fibrous layer of a bone s periosteum, where fibrous extensions called Sharpey s fibers enter into the bone s matrix. Lab Activity 1 Skeletal Muscle l.s. Skeletal Muscle in longitudinal section Lab Activity 1 Skeletal Muscle l.s. (longitudinal section) Observe a tissue preparation labeled Skeletal Muscle, l.s., or Muscle, three types. A nonparallel section makes the fibers appear short and interwoven. Skeletal muscle fibers are characterized by having distinctive cross bands called striations. The striations are produced by the alternating arrangement of proteins in the rod-like contractile elements called myofibrils. Figure 16.2 Skeletal muscle consists of long multinucleated fibers (cells). 3

4 Figure 16.3 Skeletal muscle (100x) consists of fibers (cells) that are long, parallel, and striated. Long protein contractile elements, the myofibrils, run the length of the fiber and contain thin and thick protein filaments. The alternating arrangement of thin and thick protein filaments produces the cross-bands called striations. Lab Activity 1 Skeletal Muscle l.s. (longitudinal section) Fiber Because the muscle cell resembles the structure of a fiber, (being long, thin, and cylindrical) the term fiber is substituted for cell. Myofibril Myofibrils are long parallel contractile elements that are mostly composed of the contractile proteins actin and myosin. Myofibrils are difficult to identify on most slide preparations. In longitudinal sections of muscle, the myofibrils appear as extremely thin parallel elements that have striations. The alignment of the striations of adjacent myofibrils produces the striations of the fiber. Lab Activity 1 Skeletal Muscle l.s. (longitudinal section) Striations Striations are the cross bands produced by the alternating pattern of thin and thick filaments along the length of the myofibrils. The alignment of the striations of adjacent myofibrils produces the striations of the fiber. Endomysium The endomysium is the layer of connective tissue that surrounds each individual muscle fiber. It consists mostly of reticular fibers, fibroblasts, matrix. The endomysium serves as a passageway for capillaries and nerve fibers, and transmits the contractile force from the fiber to adjacent connective tissues. Lab Activity 1 Skeletal Muscle l.s. (longitudinal section) A band The A bands are the dark cross-bands and consist mostly of protein filaments called thick filaments. The thick filaments are associated with other proteins in two regions: (1) a region called the zone of overlap, where thin filaments from the I bands overlap the thick filaments, and (2) a central region called the M line, where structural proteins align adjacent think filaments. I band The I bands are the light cross-bands. The I bands consist of protein filaments called thin filaments. The thin filaments have a central region called the Z lines (discs). Lab Activity 1 Skeletal Muscle l.s. (longitudinal section) Z lines (disks) Z lines are protein filaments located at the centers of the I bands. The Z lines connect the thin filaments of adjacent sarcomeres. Sarcomere The sarcomere is the region between two adjacent Z lines (discs). The sarcomeres are the functional units of contraction within the fiber. Figure 16.4 Skeletal muscle fiber (1,000x) showing the detail of the striations (bands) and the sarcomere. 4

5 Lab Activity 2 Skeletal Muscle x.s. Figure 16.5 Skeletal muscle fiber (1,500x) showing the bands of the fiber. Skeletal Muscle in Cross Section Lab Activity 2 Skeletal Muscle x.s. (cross section) Observe a tissue preparation labeled Skeletal Muscle, xs. A preparation of a cross section of a muscle is useful in showing the anatomy of the muscle. Exceptionally good preparations show the cross sectional detail of the individual fibers. Figure 16.6 A cross section of a muscle (40x) showing the general organization of the muscle. Lab Activity 2 Skeletal Muscle x.s. (cross section) Fibers Because the cells of muscles are long, cylindrical, and threadlike, the cells are called fibers. In cross section each fiber is seen surrounded by a thin light area of connective tissue called the endomysium. Endomysium The endomysium is the connective tissue that surrounds the muscle fibers. The endomysium merges into a layer of connective tissue the perimysium. Perimysium The perimysium is the connective tissue that surrounds a group of fibers and their associate connective tissue, the endomysium. The perimysium merges into the outer connective tissue of the muscle called the epimysium. Fascicles Fascicles are groups of fibers surrounded by a layer of connective tissue called the perimysium. Figure 16.7 Cross sections of muscle fibers as observed under oil immersion (1,500x). The small dots are cross sections of the fiber s myofibrils. Myofibrils consist mostly of the contractile proteins, actin and myosin. Regulatory and organizational proteins are also present. 5

6 Lab Activity 2 Skeletal Muscle x.s. (cross section) Myofibril Myofibrils in cross section are difficult to identify on most slide preparations. In a cross section of a muscle fiber, the myofibrils appear as extremely small dots. Myofibrils are the contractile elements that are mostly composed of the thin and thick filaments. The thin filaments house the contractile protein actin, and the thick filaments house the contractile protein myosin. Attachments of a Muscle Muscles typically have at two ends, each with one or more sites of dense fibrous connective tissue that serves as points of attachment. These points of attachment are either direct or indirect attachments and serve either as the moveable or immovable attachment sites. Direct Attachments Direct attachments occur when the epimysium of the muscle directly attaches to the periosteum of the bone or perichondrium of cartilage. Figure 16.8 The connective tissues surrounding skeletal muscle fibers are shown attached into the fibrous layer of the periosteum. Indirect Attachments Indirect attachments are more common than direct attachments. Indirect attachments occur when the epimysium of the muscle continues as a rope-like dense regular connective tissue strand called a tendon or a sheet-like layer called an aponeurosis. Figure 16.9 The connective tissues surrounding skeletal muscle fibers are shown continuing into a tendon. Tendons are rope-like structures formed of dense regular connective tissue. Tendons connect muscles into the fibrous periosteum of bone. Sharpey s fibers connect the fibrous periosteum into the matrix of bone. 6

7 Attachments Insertion A muscle s insertion is the site of attachment that moves when the muscle contracts. Origin A muscle s origin is the site of attachment that does not move when the muscle contracts. Microanatomy of a Skeletal Muscle Fiber Skeletal muscle fibers are characterized by being long, cylindrical, striated, and multinucleated Neuromuscular Junction Figure Microanatomy of a skeletal muscle fiber. A neuromuscular junction is the synapse of an axon of a motor neuron and a muscle fiber. Located at the neuromuscular junction are the terminals of the axon. The axon terminals house the presynaptic membrane. The presynaptic membrane releases a neurotransmitter (acetylcholine). The region of the sarcolemma (plasma membrane) at the neuromuscular junction that is responsive to the neurotransmitter is called the postsynaptic membrane. An action potential begins at the postsynaptic membrane and spreads over the sarcolemma. Sarcolemma The sarcolemma is the plasma membrane of the muscle fiber. In addition to functioning as the boundary of the fiber, the sarcolemma is excitable. Excitability means that the membrane can generate and conduct a signal called an action potential. Figure The neuromuscular junction is the union of an axon of a motor neuron and the sarcolemma of a muscle fiber. 7

8 Figure The sarcolemma is an excitable membrane; it generates and conducts an action potential. Sarcoplasm and T Tubules Sarcoplasm Sarcoplasm is the cytoplasm of the muscle fiber. Transverse tubules (T tubules) Transverse tubules (T tubules) are small excitable tubules continuous with the sarcolemma and in close association with the terminal cisternae of the sarcoplasmic reticulum. Each T tubule is located between two terminal cisternae forming a unit called a triad. T tubules wrap around the myofibrils and conduct action potentials from the sarcolemma into the interior of the fiber. T tubules contain extracellular fluid. Figure Transverse tubules (T tubules) are small excitable tubules continuous with the sarcolemma and in close association with the terminal cisternae of the sarcoplasmic reticulum. Sarcoplasmic Reticulum The sarcoplasmic reticulum is a system of tubes and membranes that wraps around each myofibril and is in close association with the T tubules. On each side of a transverse tube the network of smaller tubules of the sarcoplasmic reticulum merges into chambers called the terminal cisternae. Thus, at the side of each T tubule there is a terminal cisterna; the complex forming a unit called a triad. Similar to the endoplasmic reticulum of nucleated cells, in muscle fibers the sarcoplasmic reticulum takes on an additional role of calcium ion regulation. Calcium ion membrane pumps of the sarcoplasmic reticulum actively remove calcium ions from the sarcoplasm for storage in the terminal cisternae. Thus, resting muscle fibers have a low level of calcium ions in their sarcoplasm. The arrival of an action potential by way of the T tubules results in opening the terminal cisternae calcium ion channels. Calcium ions then diffuse into the sarcoplasm and initiate contraction. Figure The sarcoplasmic reticulum is a system of tubes and membranes that wraps around each myofibril and is in close association with the transverse tubules. At the side of each T tubule there is a terminal cisterna; the complex forming a unit called a triad. Myofibrils Myofibrils are long parallel contractile elements that are mostly composed of the contractile proteins, myosin and actin, organized in the thick and thin filaments, respectively. The arrangement of the contractile proteins produces cross-bands called striations. The dark bands are called the A bands, and the light bands are called the I bands. Also, associated with the myofibrils are regulatory proteins, troponin and tropomyosin, and elastic filaments called titin. Troponin and tropomyosin are associated with the thin filaments are regulate contraction by blocking the interaction of myosin with actin. Titin filaments extend from the Z lines (discs) into the thick filaments and function in the organization and the alignment of the thin and thick filaments. 8

9 A bands Figure Microanatomy of myofibrils. Myofibrils are arranged into I bands and A bands. The A band is a dark band and is organized into (1) thick filaments, (2) bare zone, (3) an M line, (4) a zone of overlap, and (5) H zone. A Bands - Thick filaments The thick filaments are composed of the contractile protein myosin. A myosin molecule consists of two regions, a tail and a head. The myosin head binds to the contractile protein actin, and once bound pivots to produce contractile force. Many myosin molecules are united to form a thick filament. The myosin molecules of a thick filament are arranged so that the heads occupy the end regions leaving a central bare zone. In the center of the thick filament a line called the M line joins adjacent thick filaments. A portion of the A band additionally contains thin filaments. The region where the thin filaments overlap the thick filaments is called the zone of overlap. The region of the A band where the thin filaments are not located is called the H zone. Figure Thick filaments are composed of the contractile protein myosin. A myosin molecule consists of two regions, a tail and a head. Many myosin molecules are united to form a thick filament. I Bands The I band is the light band and is organized into (1) thin filaments, (2) G actin, (3) F actin, (4) troponin, (5) tropomyosin, (6) Z lines. The thin filaments are composed of the contractile protein actin. Actin molecules are globular in shape (G actin) and are organized into filament strands (F actin). Each molecule of actin has a myosin binding site (an active site). A portion of the thin filament extends into the A band forming the region called the zone of overlap. In a resting fiber, the myosin binding sites are covered by the troponin-tropomyosin complex and the overlapping filaments are blocked from interaction. Troponin - I Bands Troponin consists of three subunits. One of the subunits binds troponin to tropomyosin producing the troponin-tropomyosin complex. Another subunit binds the troponin-tropomyosin complex to G actin in a position that causes the troponin-tropomyosin complex to block the myosin binding sites (active sites). The third subunit binds to calcium ions. In the resting muscle fiber calcium ions are stored in the terminal cisternae and this site is open. 9

10 I Bands Movement of Troponin-Tropomyosin Complex Figure The I band is the light band and is organized into (1) thin filaments, (2) G actin, (3) F actin, (4) troponin, (5) tropomyosin, (6) Z lines. The myosin binding sites (active sites) are blocked by the troponintropomyosin complex due to the unavailability of ionic calcium. When the terminal cisternae depolarize, calcium ions are released into the sarcoplasm and bind to troponin. Binding of calcium ions to troponin results in a movement of the troponin-tropomyosin complex from its blocking position on the myosin binding site (active site). This allows myosin to bind to actin and contraction begins. Sarcomere Figure Ionic calcium bonds to troponin resulting the movement of the troponintropomyosin complex from the myosin binding sites (active sites). The sarcomere is the functional unit of contraction of the muscle fiber. A sarcomere is the region between adjacent Z lines (discs). Structurally, a sarcomere includes one-half of an I band, the A band, and one-half of the adjacent I band. When a fiber contracts, the myosin (thick filaments) pulls the actin (of the thin filaments) inward. Thus, the sarcomeres shorten as the I bands decrease in length. Figure Availability of ionic calcium results in the removal of the blocking action of troponintropomyosin complexes. Contraction results in a shortening of the sarcomeres as the I bands decrease in length as the thin filaments (actin) are pulled toward the center of the A band. Innervation of the Muscle Fiber Neuromuscular junctions and Muscle Spindles 10

11 Muscle Spindles - Proprioceptors Muscle contraction is controlled by the central nervous system (the brain and spinal cord) by motor neurons. To control muscle contraction the central nervous system depends upon sensory input from a class of receptors called proprioceptors, receptors that receive stimuli from within the body. Figure Muscle contraction is controlled by motor neurons in the central nervous system, the brain and spinal cord. In order for the central nervous system to control muscle contraction, it depends upon sensory input from a class of receptors called proprioceptors. Proprioceptors For monitoring muscles, proprioceptors are commonly located in within muscles, joints, and in their associated connective tissues. Thus, these proprioceptors provide the central nervous system with information as to the position of the body s parts in reference to neighboring parts. The muscle spindles found scattered among a muscle s contractile fibers, in addition to monitoring contraction, respond to muscle stretch and function in reflex responses. Lab Activity -3 Proprioceptors Muscle Spindle Observe a slide preparation labeled Muscle spindles. Muscle spindles will be observed as small sensory structures ( specialized fibers ) located parallel to the long abundant contractile muscle fibers. Figure This preparation (40x) shows both muscle spindles (sensory) and neuromuscular junctions (motor). Information from muscle spindles and other proprioceptors is used to determine the position of the body s parts. Motor neurons of the central nervous system form unions with skeletal muscles, the neuromuscular junctions, to control muscle contraction. Figure A muscle spindle (430x) is shown located among the contractile muscle fibers. Muscle spindles function as proprioceptors and additionally respond to stretch and function in reflex responses. 11

12 Neuromuscular Junction Effector Site Axons of motor neurons leave the central nervous system and terminate at muscle fibers forming specialized unions called neuromuscular junctions (NMJs). Figure Sensory information from proprioceptors is integrated within the central nervous system and a response is initiated by motor neurons Neuromuscular Junction Effector Site A neuromuscular junction is the union between a motor neuron and a muscle fiber. As the axon from the motor neuron approaches the plasma membrane (sarcolemma) of the muscle fiber it forms many branches that end in knob-like structures called axon terminals. Each axon terminal (presynaptic membrane) and its associated region of the muscle fiber s plasma membrane (postsynaptic membrane) forms a chemical synapse. The axon terminals release the neurotransmitter acetylcholine. The postsynaptic membrane houses acetylcholine receptors (and associated ion channels). Figure A neuromuscular junction is the union between a motor neuron and a muscle fiber. Lab Activity 4 Neuromuscular Junctions Observe a slide preparation labeled Neuromuscular junctions, Myoneural junctions, or Motor end plates. These preparations are whole mounts of skeletal muscle fibers with their associated motor axons forming unions with the fibers at neuromuscular junctions. Neuromuscular Junctions Chemical Synapse Neuromuscular junctions are the sites of chemical synapses between the motor neuron and the sarcolemma of the muscle fiber. A synapse is the site of communication between neurons or neurons and effector cells, such as muscles and glands. A chemical synapse involves the following components: Presynaptic neuron (membrane) Synaptic cleft Postsynaptic cell (membrane) 12

13 Neuromuscular Junctions Chemical Synapse Presynaptic neuron (membrane) The presynaptic neuron houses a membrane that is involved in the release of a neurotransmitter. At the neuromuscular junction, the axon terminals house presynaptic membrane that is involved in the release of the neurotransmitter acetylcholine. Synaptic cleft The synaptic cleft is a space between the presynaptic membrane and the postsynaptic cell (membrane). The synaptic cleft is a minute cleft where the neurotransmitter rapidly diffuses across to the postsynaptic cell (membrane). Neuromuscular Junctions Chemical Synapse Postsynaptic cell (membrane) The postsynaptic cell (membrane) houses receptors for the neurotransmitter. When bound with a neurotransmitter, receptors allow the passage of ions, thus, changing the transmembrane potential of the postsynaptic cell. At the neuromuscular junction, the receptors are located at the postsynaptic membrane. The receptors bind acetylcholine, which results in the opening of sodium ion channels. Once the sodium channels open, sodium ions diffuse from the extracellular fluid resulting in a depolarization at the postsynaptic membrane.the depolarization results in a wave of electrical excitation, an action potential, that spreads over the sarcolemma. Neuromuscular Junctions Figure A neuromuscular junctions is the site of a chemical synapse between a motor neuron and the sarcolemma of the muscle fiber. Neuromuscular junctions Neuromuscular junctions are the unions of the axons of motor neurons and the muscle fibers. Each neuromuscular junction consists of numerous synapses formed at each axon terminal (presynaptic membrane) and its associated plasma membrane (the sarcolemma of the muscle fiber) the postsynaptic membrane. Axon of motor neuron Axons of motor neurons are long extensions from the body of the motor neuron (in central nervous system) that forms unions with muscle fibers called neuromuscular junctions. Axon terminals Axon terminals are the specialized ends of an axon. Each axon terminal forms a portion of a synapse and houses the presynaptic membrane. Presynaptic membrane releases a neurotransmitter. At the neuromuscular junction, the neurotransmitter is acetylcholine(ach). CONTRACTION OF SKELETAL MUSCLE FIBER Contraction of a skeletal muscle fiber involves excitationcontraction coupling. Contraction of Skeletal Muscle Fiber Excitation Excitation involves the events starting with the arrival of a stimulus (nerve impulse) at the neuromuscular junction and ends with the depolarization of the terminal cisternae, which results in the release of calcium ions. Contraction Contraction begins with the exposure of the myosin binding (active) sites of actin, the binding of myosin, and the movement of the (thin filaments) inward toward the centers of the A bands. This sliding of the filaments, called the sliding filament theory, explains how the thin filaments move inward along the thick filaments. 13

14 Neuromuscular Junction Excitation of Sarcolemma Motor neurons in the central nervous send their axons by way of nerves to form specialized unions with skeletal muscle fibers called neuromuscular junctions (also called myoneural junctions, or motor end plates). Figure Sensory information from proprioceptors is integrated and analyzed by the central nervous system. Motor neurons send axons to muscle fibers and form unions called neuromuscular junctions. Events at the Neuromuscular Junction Arrival of Action Potential (nerve impulse) The arrival of an action potential at an axon terminal triggers the opening of calcium ion channels within its plasma membrane. Calcium ions diffuse into the axon terminal and promote the fusion of vesicles and the exocytosis of the neurotransmitter acetylcholine (ACh). Acetylcholine released at the axon terminal s presynaptic membrane diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane (of the sarcolemma). Events at the Neuromuscular Junction The binding of acetylcholine to its receptors results in the opening of sodium ion channels and the rapid diffusion of sodium ions into the cell. The inward movement of sodium ions causes a depolarization of the postsynaptic membrane, which spreads along the sarcolemma as an action potential. The excitation events at the neuromuscular junction are rapid and brief. Acetylcholine is rapidly broken down by the enzyme acetylcholinerase (AChE) and the synapse is returned to its initial state, ready to respond to the arrival of another action potential. Figure Excitation events begin at the neuromuscular junction with the arrival of an action potential. Depolarization of Sarcolemma and T tubules Movement of troponin-tropomyosin complex As the action potential spreads over the sarcolemma, the T tubules are also depolarized. Depolarization of the T tubules results in a rapid stimulation of the associated terminal cisternae (a T tubule and two associated terminal cisternae are a triad). The terminal cisternae respond by releasing calcium ions into the sarcoplasm. Calcium ions bond to troponin, and troponin changes its shape. As a result, the troponin-tropomyosin complex moves from its blocking position on the myosin binding sites (active sites) of actin. Exposure of the myosin binding sites of actin allows myosin to bind. The interaction of myosin with actin results in the inward sliding of the thin filaments. 14

15 Contraction of the Muscle Fiber Sliding Filament Theory Figure Excitation results in the removal of the troponin-tropomyosin complex from blocking the myosin binding sites (active sites) on actin. Exposure of the myosin binding sites of actin allows myosin to bind. The interaction of myosin with actin results in the inward sliding of the thin filaments. Contraction of the Muscle Fiber Sliding Filament Theory The sliding filament theory of muscle fiber contraction states that the thin and thick filaments do not shorten during contraction. Instead, the filaments slide past one another. More specifically, the thin filaments slide inward as the heads (cross-bridges) of the thick filaments (myosin) pull actin inward. A molecule of myosin exists in either a high energy configuration or a low energy configuration. Contraction of the Muscle Fiber Energy of Myosin High energy state of myosin In the high energy state, myosin has bound with the energy rich molecule, ATP (ADP and phosphate remain bound at the head). In this state, the head of myosin is in a position that extends away from the center of the A band, the M line. Low energy state of myosin In the low energy state, myosin has reacted with actin, and the head of myosin has moved (pivoted) to a position toward the center of the A band, the M line. ADP and phosphate are released from myosin. The pivoting of the head is an expression of mechanical energy (derived from the chemical energy in the breakdown of ATP). Contraction of the Muscle Fiber Figure The heads (cross-bridges) of myosin exist in either a high energy configuration or a low energy configurations. Binding of ATP produces the high energy configuration, and the myosin heads are positioned away from the M line. Binding of the myosin heads to actin results in the pivoting of the heads to the low energy configuration. In this position the myosin heads are positioned toward the M line. Once the troponin-tropomyosin complex moves away from its blocking position on actin, the high energy heads of myosin (cross-bridges) bind to actin, and the process of the inward sliding of the thin filaments initiated. The heads (cross-bridges) of myosin, now attached to actin, pivot toward the M line (center of the A band). The pivoting of a myosin head with the associated pulling of actin (the thin filament) inward toward the M line is called the power stroke. Upon completion of the power stroke and still attached to actin, the myosin heads are in a low energy configuration. The myosin heads now binds with ATP and capture its chemical energy. 15

16 Utilization of ATP has two results. The first result is the detachment of the low energy myosin heads (cross-bridges) from actin. Once detached, the second event, the reactivation of the myosin heads (cross-bridges) to their high energy state, occurs. The reactivation of the myosin heads (cross-bridges) results in their heads facing away from the M line, now ready to bind with actin that has been pulled into position by the preceding power stroke. Binding of high energy myosin heads (cross-bridges), power strokes, and reactivation of myosin heads (crossbridges) by ATP, will continue until the troponintropomyosin complex moves back to a blocking position covering the myosin binding sites (active sites) of actin. Figure Contraction begins when high energy myosin heads (cross-bridges) pull on actin. Each head produces a power stroke as it pivots and pulls its associated actin (thin filament) inward toward the M line (center of A band). Binding of high energy myosin heads (cross-bridges), power strokes, and reactivation of myosin heads (crossbridges) by ATP, will continue until the troponin-tropomyosin complex moves back to a blocking position. Filament Alignments The number of active cross-bridges and the position of the thin filaments within the A band are two factors that influence the tension that is produced by a contracting fiber. Maximal tension is produced when a fiber begins contracting from an alignment established at the normal resting length (Figure A). This alignment allows maximal cross-bridge interaction (thin filaments with thick filaments) along with the maximal inward sliding of the thin filaments. When a fiber is in an alignment produced by a strong contraction (Figure B), the Z lines (discs) contact the ends of the thick filaments and the thin filaments touch at the M line. This alignment results in a decrease of muscle tension. A decrease of muscle tension is also seen when the fiber is in an overextended alignment due to being stretched (Figure C). Stretching pulls the thin filaments away from the A band resulting in reduction of active cross-bridges. Figure Varying the alignment of the thin filaments within the A bands results in the production of different amounts of tension. An alignment of the thin filament that permits maximal cross-bridge interaction along with the maximal inward sliding of the thin filaments produces maximal tension. A reduction in tension is seen in fibers that are either stretched or contracted beyond the ideal operating length. Relaxation Reabsorption of calcium ions into the sarcoplasmic reticulum (SR), results in low calcium levels in the sarcoplasm and the return of the troponin-tropomyosin complexes to their blocking position. Once myosin binding sites are blocked, the muscle fiber is in a state of relaxation. Figure Reabsorption of calcium ions into the sarcoplasmic reticulum (SR), results in low levels of calcium in the sarcoplasm. This results in the return of the troponin-tropomyosin complex to its blocking position. 16

17 Twitch The regulation of the concentration of ionic calcium in the sarcoplasm is essential for the control of muscle contraction and relaxation. The sarcoplasmic reticulum continually pumps ionic calcium out of the sarcoplasm and maintains a low sarcoplasm level. Release of ionic calcium into the sarcoplasm by stimulation of the terminal cisternae triggers contraction as calcium ions bind with troponin resulting in movement of the troponintropomyosin complex from its normal blocking position on actin. Because calcium ions are continually being reabsorbed by the sarcoplasmic reticulum, a single stimulus (nerve impulse) produces a brief contractile event unless the terminal cisternae are stimulated again. A single stimulus producing a brief single contraction-relaxation of a muscle fiber is called a twitch. Muscle activity can be graphically recorded as a tracing called a myogram. Figure Myogram of a typical twitch. A twitch results when a single stimulus produces a brief single contraction-relaxation of a muscle fiber. Twitch Latent Period Latent Period The latent period is the time from the arrival of the nerve impulse at the synapse (a neuromuscular junction) to the release of calcium from the sarcoplasmic reticulum. Sequentially, the latent period involves the following processes: (1) begins with the depolarization of the sarcolemma at the synapse (a neuromuscular junction), (2) the spread of the depolarization over the sarcolemma, (3) the depolarization of the T tubules, and the (4) stimulation of the terminal cisternae with the release of calcium ions into the sarcoplasm. Twitch Contraction Phase Contraction Phase The contraction phase begins with the (1) binding of calcium ions to troponin, (2) the movement of the troponin-tropomyosin complex, and (3) continues with the sliding of the thin filaments, which results from power strokes at the cross-bridges. Power strokes are the pivoting of the high energy myosin heads (cross-bridges) with the pulling of attached actin molecules (thin filaments) inward toward the M line (center of A band). Once the heads have pivoted and pulled actin inward, they are in a low energy position and binding of ATP to the myosin heads (cross-bridges) occurs. The utilization of ATP results in the release of myosin from actin and the reactivation of the myosin head to its high energy position. Twitch Velocity Not all muscle fibers twitch at the same speed. Depending upon the physiological aspects of the fiber, especially the primary way the fiber catabolizes fuel molecules (glycolysis vs. aerobic metabolism), the speed of twitches varies from fast (glycolysis) to slow (aerobic). Fast twitch fibers provide rapid movements and are found, for example, in the extrinsic muscles of the eye and in the eyelid. Intermediate and slow twitch fibers are more fatigue resistant and are found, for example, in large leg muscles such as the muscles of the calf (soleus and gastrocnemius). Twitch Relaxation Phase Relaxation Phase The relaxation phase begins as calcium ion reabsorption by the sarcoplasmic reticulum starts to lower the availability of calcium ions in the sarcoplasm. As calcium ions begin to dissociate from troponin, the troponintropomyosin complexes begin to move back into blocking the binding sites (the active sites) on actin. The relaxation phase continues until the blocking of the active sites on actin returns the muscle fiber to its original resting state. 17

18 Muscle Responses Figure Myogram showing the relative speed of twitches of different muscles. Depending upon the physiological aspects of the fiber, especially the amount and rate of enzyme activity, the speed of twitches varies from slow to fast. Varying the Contraction by Motor Unit Recruitment Varying the Contraction by Motor Unit Recruitment Varying the degree of muscle contraction, called a graded response, is important in producing the required contraction for a movement. One way a muscle s response is graded is by the nervous system recruiting more muscle fibers into the contractile event (movement). The axon from the cell body of a motor neuron in the central nervous system may branch and innervate from a few to many muscle fibers. Each motor neuron and the muscle fibers it innervates are called a motor unit. In a contractile response of a muscle, increasing the number of contracting motor units increases the tension of the muscle. Varying the Contraction by Motor Unit Recruitment The following myogram supports the relationship between increasing the number of stimulated fibers and muscle tension. The myogram shows the effect of stimulating a muscle with increasing voltages. As voltage is increased from zero, a voltage is reached where the most irritable fibers of the muscle contract. The voltage that produces the initial contraction is the threshold stimulus (voltage). Any voltage stimuli that are less than threshold is a subthreshold stimulus and does not produce a contraction. As the voltage of the stimuli is increased above the threshold, muscle contractions show increasing tension. Increasing voltage stimulates more and more of the muscle s fibers until all fibers are stimulated. At the point of stimulation where all of the muscle s fibers are stimulated the muscle produces maximal tension. The voltage that produces maximal tension is the maximal stimulus. Increasing the voltage beyond this point has no effect on the tension of the muscle s contraction as all fibers have already been stimulated. Figure Myogram showing the relationship between increasing the number of muscle fibers and increased muscle tension. Lab Activity 5 Neuromuscular Junctions Observe a slide preparation labeled Neuromuscular junctions, Myoneural junctions, or Motor end plates. These preparations are whole mounts of skeletal muscle fibers with their associated motor axons forming unions with muscle fibers at neuromuscular junctions. 18

19 Figure A motor unit consists of a motor neuron and the muscle fibers it innervates. Recruitment of motor units increases the force of contraction. Lab Activity 5 Neuromuscular Junctions As the motor axons enter the muscle many branches of the axons can be observed. Follow an axon as it branches, each branch forming a neuromuscular junctions with a different muscle fiber. A motor neuron and the muscle fibers it innervates are called a motor unit. Success with identification of motor units depends upon the quality of the slide preparation, especially, the presence of long branching motor axons. Figure Muscle fibers showing organization into motor units. Notice that in this preparation, each fiber receives only one neuromuscular junction and from only one motor unit. Treppe- Staircase Effect or Staircase Phenomenon Treppe is a progressive series of increasing stronger contractions of a resting muscle, where each contraction results from a stimulus of the same intensity.. Treppe results from the increased ability of the muscle s fibers to respond to subsequent stimuli due to the (1) increased efficiency of enzyme systems, (2) increased calcium ion availability, and (3) increased heat. Isotonic and Isometric Contractions Figure Myogram of treppe showing the effect of stimulating a muscle with stimuli of the same intensity and applying each stimulus immediately after the muscle has completed each relaxation phase. 19

20 Isotonic Contraction An isotonic muscle contraction is a contraction that results in a change of the length of the muscle along with movement of the load. In an isotonic contraction, once the muscle has developed the tension required to move the load (overcomes resistance), the tension remains constant throughout the contraction. There are two types of isotonic contractions: (1) concentric and (2) eccentric. Concentric Isotonic Contraction A concentric contraction is a contraction that results in the shortening of the muscle along with the movement of the load. An example of concentric contraction is seen in an arm-wrestling match as the winning person moves the opponent s arm toward the top of the table. Eccentric Isotonic Contraction Figure A concentric isotonic contraction produces tension that overcomes the resistance (load). The muscle shortens with its tension remaining constant throughout the contraction. An eccentric contraction is a contraction that occurs while a muscle lengthens. In an eccentric contraction the muscle does not develop enough tension to overcome the load (resistance). Thus, even though the muscle is contracting, it is lengthening because the load, such as a stronger contracting muscle, is stretching the muscle. An example of eccentric contraction is seen in an arm-wrestling match as the losing person s arm is being pushed toward the table top. The losing person cannot overcome the resistance (opponent) and their contracting muscle lengthens as it moves toward the table top. Isometric Contraction Figure A eccentric isotonic contraction produces tension but cannot overcome the resistance (load). The muscle lengthens while its tension remains constant throughout the contraction An isometric contraction is a contraction where the muscle does not change length because it does not develop enough tension to overcome the resistance (load). An example of concentric contraction is seen in an arm-wrestling match when the arms of the two opponents are locked in a fixed position, as neither person can overcome the opposing resistance. 20

21 Muscle Responses Varying the Contraction by Frequency of Stimulation Figure An isometric contraction is a contraction where the muscle does not change length as it does not develop enough tension to overcome the resistance (load). Varying the Contraction by Frequency of Stimulation In addition to motor unit recruitment, another way muscle contraction can be graded (varied) is to change the frequency (rate) of muscle stimulation. The frequency (rate) of muscle stimulation varies from producing a brief single contraction to a sustained forceful contraction called tetanus. Wave Summation (summation of twitches) and Tetanus A twitch is the single brief contraction of a muscle fiber (cell) that results from a single stimulus. Since the functional units of whole muscles are muscle fibers (cells) the term twitch can be expanded and used in reference to the contraction of a whole muscle. This is especially useful in laboratory studies when the contractions of whole muscles are studied by applying controlled (voltage and frequency) electrical stimuli. Thus, in the following descriptions reference is to whole muscles because whole muscles exhibit the contractile characteristics of the individual fibers (cells). Wave Summation If another stimulus is applied in rapid succession to a muscle (after the refractory period), the muscle will immediately enter another phase of contraction. The following contraction produces more tension than the preceding contraction. Thus, the fiber is maintained in a state of contraction for a longer period of time. This maintenance of tension due to the rapid succession of stimuli is called wave (temporal) summation. Incomplete Tetanus Incomplete tetanus (incomplete wave summation) is produced by rapid successive contraction-relaxation phases of the muscle. Incomplete tetanus is characterized by as sustained contraction with the muscle quivering as it rapidly undergoes contraction phases, each followed by a brief relaxation phase. If the frequency of successive stimuli is increased, the phases of relaxation continue to shorten and finally disappear as the muscle enters complete tetanus, or a sustained contraction. 21

22 Complete Tetanus Complete tetanus results when the stimuli arrive at a frequency (rate) that does not allow relaxation. In complete tetanus stimuli are arriving so quickly that the sarcoplasmic reticulum does not have time to reabsorb calcium ions. Calcium levels remain high resulting in maximal unblocking of actin and myosin (cross-bridge) interactions. Figure Myograms showing how a muscle can be modified into a sustained contraction by increasing the frequency (rate) of stimuli. Lab Activity 6- Increasing Frequency of Stimulation Frog Gastrocnemius Muscle Because laboratories are supplied with a variety of instrumentation for the stimulation and recording of muscle contraction, the topic of instrumentation and setup is not covered. This activity is limited to the interpretation of typical myograms from muscle stimulation and contraction exercises. Figure Myogram of a frog gastrocnemius muscle showing the effect of increasing the frequency (rate) of stimulation. MUSCLE ENERGETICS Figure Myogram from an isolated frog gastrocnemius muscle showing the effect of increasing and the frequency of stimulation and resulting muscle fatigue. Muscle Fiber - Resting The sources of energy for resting muscle fibers include fatty acids and glucose. 22

23 Fatty Acids Fatty acid catabolism provides most of the energy (about 95%) for the resting muscle cell. Fatty acids from the blood enter the sarcoplasm (cytoplasm) of the muscle cell. Then they enter into the mitochondria where their energy is used in the TCA (tricarboxylic acid cycle), or Krebs cycle, and the electron transport system to drive the reaction ADP + Pi > ATP. In the final step of mitochondrial catabolism, oxygen is combined with protons (hydrogen ions) and electrons to form water. Thus, because oxygen is used in this phase of catabolism, it is aerobic metabolism. In this process of ATP production carbon dioxide and water are produced as waste products. Fatty Acids A small quantity of ATP produced in a resting muscle fiber remains in the sarcoplasm and is considered stored ATP. Stored ATP is an immediate source of energy, especially for a quick response in muscle contraction. ATP is also used in the formation of energy rich creatine phosphate (ATP + creatine > ADP + creatine phosphate). Creatine, a product formed from the amino acids arginine and glycine, is phosphorylated (through the action of the enzyme creatine phosphokinase) to produce the high energy molecule creatine phosphate. Glucose Another source of energy for resting muscle cells is glucose. However, the major utilization of glucose is in the production of glycogen. Glycogen is produced by combining molecules of glucose into long branching chains. Thus, glycogen is a polysaccharide stored in the sarcoplasm of the muscle cell, and is used as a source of energy during a muscle fiber s rapid response and in prolonged exercise. Figure In a resting muscle fiber, the major source of energy for the production of ATP is from the catabolism of fatty acids. A small amount of ATP is stored. Additionally, ATP is used to form stored sources of energy, glycogen and creatine phosphate. MUSCLE ENERGETICS Muscle Fiber Moderate Prolonged Activity Muscle Fiber - Moderate Prolonged Activity As a muscle fiber begins contraction, any stored ATP is immediately utilized. The catabolism of fatty acids continues, but cannot provide the required amount of ATP. Two other sources of energy are catabolized to meet higher energy requirements creatine phosphate and glucose. 23