Week 6 - Muscles and Muscle Tissue PDF

Muscles and Muscle Tissue The learning outcome: • • • • • • • • The three types of muscle tissue-skeletal, cardiac, and smooth Characteristics of Muscle Tissue Compare and contrast the three basic types of muscle tissue List four important functions of muscle tissue. Describe t he gross structure...

Muscles and Muscle Tissue The learning outcome: • • • • • • • • The three types of muscle tissue-skeletal, cardiac, and smooth Characteristics of Muscle Tissue Compare and contrast the three basic types of muscle tissue List four important functions of muscle tissue. Describe t he gross structure of a skeletal muscle. Skeletal muscle fibers contain calcium-regulated molecular motors Sliding Filament Model of Contraction Describe factors that influence the force, velocity, and duration of skeletal muscle contraction. • Describe three types of skeletal muscle fibers and explain the relative value of each type • consider smooth muscle more briefly, largely by comparing it with skeletal muscle. Some terminology • Skeletal and smooth muscle cells (but not cardiac muscle cells) are elongated, and are called muscle fibers. • Whenever you see the prefixes Myo or Mys (both are word roots meaning "muscle") or Sarco (flesh), the reference is to muscle. For example, the plasma membrane of muscle cells is called the sarcolemma literally, "muscle" (sarco) "husk" (lemma), and muscle cell cytoplasm is called sarcoplasm. Skeletal Muscle • Skeletal muscle tissue is packaged into the skeletal muscles, organs that attach to and cover the skeleton. • Skeletal muscle fibers are the longest muscle cells and have obvious stripes called striations. Although it is often activated by reflexes, skeletal muscle is called voluntary muscle because it is the only type subject to conscious control. • When you think of skeletal muscle tissue, the key words to keep in mind are skeletal, striated, and voluntary. • Skeletal muscle is responsible for overall body mobility. It can contract rapidly, but it tires easily and must rest after short periods of activity. Nevertheless, it can exert tremendous power. • Skeletal muscle is also remarkably adaptable. For example, your forearm muscles can exert a force of a fraction of an ounce to pick up a paper clip--or a force of about 6 pounds to pick up this book! Skeletal Muscle Thin filament (Actin) Binds Oxygen Myoglobin Thick filament (Myosin) Myofibril Muscle Fiber Sarcoplasmic Reticulum Stores Ca2+ Fascicle Muscle Belly Cardiac Muscle • Cardiac muscle tissue occurs only in the heart, where it constitutes the bulk of the heart walls. • Like skeletal muscle cells, cardiac muscle cells are striated, but cardiac muscle is not voluntary. • Indeed, it can and does contract without being stimulated by the nervous system. • Most of us have no conscious control over how fast our heart beats. • Key words to remember for cardiac muscle are cardiac, striated, and involuntary. • Cardiac muscle usually contracts at a fairly steady rate set by the heart's pacemaker, but neural controls allow the heart to speed up for brief periods, as when you race across the tennis court to make that overhead smash. Smooth Muscle • Smooth muscle tissue is found in the walls of hollow visceral organs, such as the stomach, urinary bladder, and respiratory passages. • Its role is to force fluids and other substances through internal body channels. • Smooth muscle also forms valves to regulate the passage of substances through internal body openings, dilates and constricts the pupils of your eyes, and forms the arrector pili muscles attached to hair follicles. • Like skeletal muscle, smooth muscle consists of elongated cells, but smooth muscle has no striations. Like cardiac muscle, smooth muscle is not subject to voluntary control. Its contractions are slow and sustained. • We can describe smooth muscle tissue as visceral, non-striated, and involuntary. Characteristics of Muscle Tissue What enables muscle tissue to perform its duties? Four special characteristics are key. • Excitability, also termed responsiveness, is the ability of a cell to receive and respond to a stimulus by changing its membrane potential. In the case of muscle, the stimulus is usually a chemical-for example, a neurotransmitter released by a nerve cell. • Contractility is the ability to shorten forcibly when adequately stimulated. This ability sets muscle apart from all other tissue types. • Extensibility is the ability to extend or stretch. Muscle cells shorten when contracting, but they can be stretched, even beyond their resting length, when relaxed. • Elasticity is the ability of a muscle cell to recoil and resume its resting length after stretching. Muscle Functions Muscles perform at least four important functions for the body: • Produce movement. Skeletal muscles are responsible for all locomotion and manipulation. They enable you to respond quickly to jump out of the way of a car, direct your eyes, and smile or frown. Blood courses through your body because of the rhythmically beating cardiac muscle of your heart and the smooth muscle in the walls of your blood vessels, which helps maintain blood pressure. Smooth muscle in organs of the digestive, urinary, and reproductive tracts propels substances (foodstuffs, urine, semen) through the organs and along the tract. • Maintain posture and body position. Skeletal muscles function almost continuously to maintain your posture, making one tiny adjustment after another to keep your body upright. Skeletal muscle is also important for holding your bones in the correct position and prevents your joints from dislocating. • Stabilize joints. Even as they pull on bones to cause movement, they strengthen and stabilize the joints of the skeleton. • Generate heat. Muscles generate heat as they contract, which plays a role in maintaining normal body temperature A skeletal muscle is made up of muscle fibers, nerves, blood vessels, and connective tissues Nerve and Blood Supply • In general, one nerve, one artery, and one or more veins serve each muscle. • These structures all enter or exit near the central part of the muscle and branch profusely through its connective tissue sheaths. • Unlike cells of cardiac and smooth muscle tissues, which can contract without nerve stimulation, every skeletal muscle fiber is supplied with a nerve ending that controls its activity. • Skeletal muscle has a rich blood supply. This is understandable because contracting muscle fibers use huge amounts of energy and require almost continuous delivery of oxygen and nutrients via the arteries. • Muscle cells also give off large amounts of metabolic wastes that must be removed through veins if contraction is to remain efficient. • Capillaries, take a long and winding path through muscle, and have numerous cross-links, features that accommodate changes in muscle length. They straighten when the muscle stretches and twist when the muscle contracts. Connective Tissue Sheaths • In an intact muscle, there are several different connective tissue sheaths. Together these sheaths support each cell and reinforce and hold together the muscle, preventing the bulging muscles from bursting during exceptionally strong contractions. • Epimysium: is an "overcoat" of dense irregular connective tissue that surrounds the whole muscle. Sometimes it blends with the deep fascia that lies between neighboring muscles or the superficial fascia deep to the skin. • Perimysium and fascicles: Within each skeletal muscle, the muscle fibers are grouped into fascicles that resemble bundles of sticks. Surrounding each fascicle is a layer of dense irregular connective tissue called perimysium • Endomysium: is a wispy sheath of connective tissue that surrounds each individual muscle fiber. It consists of fine areolar connective tissue. Connective tissue sheaths of skeletal muscle: Epimysium, Perimysium, and Endomysium. Attachments • Most skeletal muscles span joints and attach to bones (or other structures) in at least two places. When a muscle contracts, the movable bone, the muscle's insertion, moves toward the immovable or less movable bone, the muscle's origin. In the muscles of the limbs, the origin typically lies proximal to the insertion. Muscle attachments, whether origin or insertion, may be direct or indirect. In direct, or fleshy, attachments, the epimysium of the muscle is fused to the periosteum of a bone or perichondrium of a cartilage. In indirect attachments, the muscle's connective tissue wrappings extend beyond the muscle either as a ropelike tendon or as a sheet-like aponeurosis. The tendon or aponeurosis anchors the muscle to the connective tissue covering of a skeletal element (bone or cartilage) or to the fascia of other muscles. ***Indirect attachments are much more common because of their durability and small size. Skeletal muscle fibers contain calcium-regulated molecular motors • Each skeletal muscle fiber is a long cylindrical cell with multiple oval nuclei just beneath its sarcolemma or plasma membrane. • Skeletal muscle fibers are huge cells. Their diameter typically ranges from 10 to 100 µm-up to ten times that of an average body cell- and their length is phenomenal, some up to 30 cm long. • Their large size and multiple nuclei are not surprising once you learn that hundreds of embryonic cells fuse to produce each fiber. • Sarcoplasm, the cytoplasm of a muscle cell, is similar to the cytoplasm of other cells, but it contains unusually large amounts of Glycosomes (granules of stored glycogen that provide glucose during muscle cell activity for ATP production) and Myoglobin, a red pigment that stores oxygen. Myoglobin is similar to hemoglobin, the pigment that transports oxygen in blood. • In addition to the usual organelles, a muscle cell contains three specialized structures: Myofibrils, Sarcoplasmic Reticulum, and T tubules. Basic Structure Skeletal Muscle (muscle fibre) Sarcolemma - muscle fiber plasma membrane. Transverse (T) Tubules Sarcoplasm - cytoplasm of muscle fiber. Glycogen - ATP synthesis. Myoglobin - oxygen binding Myofibrils Sarcoplasmic Reticulum Ca2+ storage Basic Structure Skeletal Muscle (muscle fibre) Striations: a repeating series of dark and light bands, are evident along the length of each myofibril. In an intact muscle fiber, the dark A bands and light I bands are nearly perfectly aligned, giving the cell its striated appearance. • Each dark A band has a lighter region in its midsection called the H zone • Each H zone is bisected vertically by a dark line called the M line (M for middle) formed by molecules of the protein Myomesin. • Each light I band also has a midline interruption, a darker area called the Z disc (or Z line). Basic Structure Skeletal Muscle (muscle fibre) https://www.youtube.com/watch?v=EdHzKYDxrKc Sarcomeres • The region of a myofibril between two successive Z discs is a sarcomere, Averaging 2 µm long, • a sarcomere is the smallest contractile unit of a muscle fiberthe functional unit of skeletal muscle. • It contains an A band flanked by half an I band at each end. • Within each myofibril, the sarcomeres align end to end like boxcars in a train. Myofilaments: • If we examine the banding pattern of a myofibril at the molecular level, we see that it arises from orderly arrangement of even smaller structures within the sarcomeres. • These smaller structures, the myofilaments or filaments, are the muscle equivalents of the Actin-containing Microfilaments and Myosin Motor Proteins The proteins actin and myosin play a role in motility and shape change in virtually every cell in the body. This property reaches its highest development in the contractile muscle fibers. There are two types of contractile myofilaments in a sarcomere: • The central thick filaments containing myosin extend the entire length of the A band . They are connected in the middle of the sarcomere at the M line. • The more lateral thin filament containing actin extend across the I band and partway into the A band. The Z disc, a protein sheet, anchors the thin filaments. Molecular Composition of Myofilaments • A hexagonal arrangement of six thin filaments surrounds each thick filament, and three thick filaments enclose each thin filament. • The H zone of the A band appears less dense because the thin filaments do not extend into this region. • The M line in the center of the H zone is slightly darker because of the fine protein strands there that hold adjacent thick filaments together. • The myofilaments are held in alignment at the Z discs and the M lines, and are anchored to the sarcolemma at the Z discs. https://www.youtube.com/watch?v=EdHzKYDxrKc Molecular Composition of Myofilaments • Muscle contraction depends on the myosin- and actin-containing myofilaments. As noted earlier, thick filaments are composed primarily of the protein myosin. • Each myosin molecule consists of six polypeptide chains: two heavy (high-molecular-weight) chains and four light chains. • The heavy chains twist together to form myosin 's rod-like tail, and each heavy chain ends in a globular head that is attached to the tail via a flexible hinge. The globular heads, each associated with two light chains, are the "business end" of myosin. • During contraction, they link the thick and thin filaments together, forming cross bridges, and swivel around their point of attachment, acting as motors to generate force. • Myosin itself splits ATP (acts as an ATPase) and uses the released energy to drive movement. • Each thick filament contains about 300 myosin molecules bundled together, with their tails forming the central part of the thick filament and their heads facing outward at the end of each molecule. As a result, the central portion of a thick filament (in the H zone) is smooth, but its ends are studded with a staggered array of myosin heads. • The thin filaments are composed chiefly of the protein actin. Actin has kidney-shaped polypeptide subunits, called Globular actin or G actin. Each G actin has a Myosin-binding Site (Or Active Site) to which the myosin heads attach during contraction. • G actin subunits polymerize into long actin filaments called filamentous, or F- actin. Two intertwined actin filaments, resembling a twisted double strand of pearls, form the backbone of each thin filament. Thin filaments also contain several regulatory proteins. • Polypeptide strands of Tropomyosin: a rod-shaped protein, spiral about the actin core and help stiffen and stabilize it. Successive tropomyosin molecules are arranged end to end along the actin filaments, and in a relaxed muscle fiber, they block myosin-binding sites on actin so that myosin heads on the thick filaments cannot bind to the thin filaments. • Troponin: , the other major protein in thin filaments, is a globular protein with three polypeptide subunits. One subunit attaches troponin to actin. Another subunit binds tropomyosin and helps position it on actin. The third subunit binds calcium ions. Both Troponin And Tropomyosin help control the myosin-actin interactions involved in contraction. Several other proteins help form the structure of the myofibril. • The elastic filament we referred to earlier is composed of the giant protein Titin. Titin extends from the Z disc to the thick filament, and then runs within the thick filament (forming its core) to attach to the M line. It holds the thick filaments in place, maintaining the organization of the A band, and helps the muscle cell spring back into shape after stretching. (The part of the titin that spans the I bands is extensible, unfolding when the muscle stretches and recoiling when the tension is released.) Tiitn DOES NOT resist stretching in the ordinary range of extension, but it stiffens as it uncoils, helping the muscle resist excessive stretching, which might pull the sarcomeres apart. • Another important structural protein is Dystrophin, which links the thin filaments to the integral proteins of the sarcolemma (Which in turn are anchored to the extracellular matrix). • Other proteins that bind filaments or sarcomeres together and maintain their alignment include Nebulin, Myomesin, and C proteins. Intermediate (Desmin) filaments extend from the Z disc and connect each myofibril to the next throughout the width of the Muscle cell. Sarcoplasmic Reticulum and T Tubules • Skeletal muscle fibers contain two sets of intracellular tubules that help regulate muscle contraction: (1) The Sarcoplasmic Reticulum and (2) T tubules. • The Sarcoplasmic Reticulum (SR) is an elaborate smooth endoplasmic reticulum. The SR regulates intracellular levels of ionic calcium. • It stores calcium and releases it on demand when the muscle fiber is stimulated to contract. • Calcium provides the final "go" signal for contraction. • Interconnecting tubules of SR surround each myofibril the way the sleeve of a loosely knitted sweater surrounds your arm. • Most SR tubules run longitudinally along the myofibril, communicating with each other at the H zone. Others called terminal cisterns ("end sacs") form larger, perpendicular cross channels at the A band-I band junctions, and they always occur in pairs. • Closely associated with the SR are large numbers of mitochondria and glycogen granules, both involved in producing the energy used during contraction. T Tubules • At each A band-I band junction, the sarcolemma of the muscle cell protrudes deep into the cell interior, forming an elongated tube called the T tubule (T for "transverse"). • The lumen (cavity) of the T tubule is continuous with the extracellular space. As a result, T tubules tremendously increase the muscle fiber's surface area. • This allows changes in the membrane potential to rapidly penetrate deep into the muscle fiber. Along its length, each T tubule runs between the paired terminal cisterns of the SR, forming triads, successive groupings of the three membranous structures (terminal cistern, T tubule, and terminal cistern). • As they pass from one myofibril to the next, the T tubules also encircle each sarcomere. Muscle contraction is ultimately controlled by nerve initiated electrical impulses that travel along the sarcolemma. • Because T tubules are continuations of the sarcolemma, they conduct impulses to the deepest regions of the muscle cell and every sarcomere. These impulses trigger the release of calcium from the adjacent terminal cisterns. • Think of the T tubules as a rapid communication or messaging system that ensures that every myofibril in the muscle fiber contracts at virtually the same time. Triad Relationships • The roles of the T tubules and SR in providing signals for contraction are tightly linked. At the triads, membrane-spanning proteins from the T tubules and SR link together across the gap between the two membranes. • The protruding integral proteins of the T tubule act as voltage sensors. • The integral proteins of the SR form gated channels through which the terminal cisterns release Ca2 + Sliding Filament Model of Contraction • We almost always think "shortening" when we hear the word contraction , but to physiologists contraction refers only to the activation of myosin's cross bridges, which are the force generating sites. • Shortening only occurs if the cross bridges generate enough tension on the thin filaments to exceed the forces that oppose shortening, such as when you lift a bowling ball. • Contraction ends when the cross bridges become inactive, the tension declines, and the muscle fiber relaxes. • In a relaxed muscle fiber, the thin and thick filaments overlap only at the ends of the A band Sliding Filament Model of Contraction • The sliding filament model of contraction states that during contraction, the thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree. Neither the thick nor the thin filaments change length during contraction. Here's how it works: • When the nervous system stimulates muscle fibers, the myosin heads on the thick filaments latch onto myosin-binding sites on actin in the thin filaments, and the sliding begins. • These cross bridge attachments form and break several times during a contraction, acting like tiny ratchets to generate tension and propel the thin filaments toward the center of the sarcomere. • As this event occurs simultaneously in sarcomeres throughout the cell, the muscle cell shortens. At the microscopic level, the following things occur as a muscle cell shortens: 1. The I bands shorten. 2. The distance between successive Z discs shortens. As the thin filaments slide centrally, the Z discs to which they attach are pulled toward the M line. 3. The H zones disappear. 4. The contiguous A bands move closer together, but their length does not change. Motor neurons stimulate skeletal muscle fibers to contract • Remember that skeletal muscle contractions are voluntary. For example, you decide when you want to contract your biceps muscle to pick up your cell phone. Making that decision involves many neurons in your brain, but the contraction of a skeletal muscle ultimately comes down to activating a few motor neurons in the spinal cord. • Motor neurons are the way that the nervous system connects with skeletal muscles and "tells" them to contract. Both neurons and muscles are excitable cells. That is, they respond to external stimuli by changing their resting membrane potential. (Remember that all cells have a resting membrane potential, which is a voltage across the plasma membrane; • These changes in membrane potential act as signals. One type of electrical signal is called an action potential (AP ; sometimes called a nerve impulse). An AP is a large change in membrane potential that spreads rapidly over long distances within a cell. Generally, APs don't spread from cell to cell. • For this reason, the signal has to be converted to a chemical signal-a chemical messenger called a neurotransmitter. That diffuses across the small gap between excitable cells to start the signal again. The neurotransmitter that motor neurons use to "tell" skeletal muscle to contract is acetylcholine or ACh. Ion Channels • Rapidly changing the membrane potential in neurons and muscle cells requires the opening and closing of membrane channel proteins that allow certain ions to pass across the membrane changes in the membrane potential • Receptors for acetylcholine are an example of this class. An ACh receptor is a single protein in the plasma membrane that is both a receptor and an ion channel. • Voltage-gated ion channels open or close in response to changes in membrane potential. They underlie all action potentials. In skeletal muscle fibers, the initial change in membrane potential is created by chemically gated channels. In other words, chemically gated ion channels cause a small local depolarization (a decrease in the membrane potential) that then triggers the voltage-gated ion channels to create an action potential. Anatomy of Motor Neurons and t he Neuromuscular Junction • Motor neurons that activate skeletal muscle fibers are called somatic motor neurons, or motor neurons of the somatic (voluntary) nervous system. • These neurons reside in the spinal cord (except for those that supply the muscles of the head and neck). Each neuron has a long threadlike extension called an axon that extends from the cell body in the spinal cord to the muscle fiber it serves. • These axons exit the spinal cord and pass throughout the body bundled together as nerves. The axon of each motor neuron branches profusely as it enters the muscle so that it can innervate multiple muscle fibers. When it reaches a muscle fiber, each axon divides again, giving off several short, curling branches that collectively form an oval neuromuscular junction, or motor end plate, with a single muscle fiber. • Each muscle fiber has only one neuromuscular junction, located approximately midway along its length. The end of the axon, called the axon terminal, and the muscle fiber are exceedingly close (5080 nm apart), but they remain separated by a space, the synaptic cleft. Which is filled with a gel-like extracellular substance rich in glycoproteins and collagen fibers. • Within the moundlike axon terminal are synaptic vesicles, small membranous sacs containing the neurotransmitter acetylcholine. The trough-like part of the muscle fiber's sarcolemma that helps form the neuromuscular junction is highly folded. These junctional folds provide a large surface area for the thousands of ACh receptors located there. • To summarize, the neuromuscular junction is like a sandwich: It is made up of part of a neuron (the axon terminals), part of a muscle cell (the junctional folds), and the "filler" between them (the synaptic cleft). 1) Events at t he neuromuscular junction: The motor neuron releases ACh that stimulates the skeletal muscle fiber, causing a local depolarization (decrease in membrane potential) called an end plate potential (EPP). 2) Muscle fiber excitation: The EPP triggers an action potential that travels across the entire sarcolemma. 3) Excitation-contraction coupling: The AP in the sarcolemma propagates along the T tubules and causes release of Ca2+ from the terminal cisterns of the SR. Ca2+ is the final trigger for contraction. It is the internal messenger that links the AP to contraction. Ca2+ binds to troponin and this causes the myosin-binding sites on actin to be exposed so that myosin heads can bind to actin. (768) Muscle Contraction - Cross Bridge Cycle, Animation. - YouTube 4) Cross bridge cycling: The muscle contracts as a result of a repeating cycle of steps that cause myofilaments to slide relative to each other. Events at t he neuromuscular junction The result of the events at the neuromuscular junction is a transient change in membrane potential that causes the interior of the sarcolemma to become less negative (a depolarization). This local depolarization is called an end plate potential (EPP) EPP spreads to the adjacent sarcolemma and triggers an AP there. After ACh binds to the ACh receptors, its effects are quickly terminated by acetylcholinesterase, an enzyme located in the synaptic cleft. Acetylcholinesterase breaks down ACh to its building blocks, acetic acid and choline. Removing ACh prevents continued muscle fiber contraction in the absence of additional nervous system stimulation. Generation of an Action Potential across the Sarcolemma -An action potential is the result of a predictable sequence of electrical changes. Once initiated, an action potential sweeps along the entire surface of the sarcolemma. -Three steps are involved in triggering and then propagating an action potential. These three steps-generation of an end plate potential followed by action potential depolarization and repolarization-During repolarization, a muscle fiber is said to be in a refractory period, because the cell cannot be stimulated again until repolarization is complete. Note that repolarization restores only the electrical conditions of the resting (polarized) state. (768) Neuromuscular Junction, Animation - YouTube -The ATP-dependent Na+ .K+ pump restores the ionic conditions of the resting state, but thousands of action potentials can occur before ionic imbalances interfere with contractile activity. A tracing of the resulting membrane potential changes Excitation-Contraction (E-C) Coupling • Is the sequence of events by which transmission of an action potential along the sarcolemma causes Myofilaments To Slide. • The action potential is brief and ends well before any signs of contraction are obvious. • The electrical signal does not act directly on the myofilaments. Instead, it causes the rise in intracellular levels of calcium ions, which triggers a sequence of events that ultimately leads to sliding of the filaments. The aftermath: -Myosin-binding sites exposed and ready for myosin binding -When the muscle AP ceases, the voltage-sensitive tubule proteins return to their original shape, closing the Ca2+ release channels of the SR. -Ca2+ levels in the sarcoplasm fall as Ca2+ is continually pumped back into the SR by Active Transport. -Without Ca2+, the blocking action of tropomyosin is restored, myosin-actin interaction is inhibited, and relaxation occurs. -Each time an AP arrives at the neuromuscular junction, the sequence of E-C coupling is repeated. Muscle Fiber Contraction: Cross Bridge Cycling • Cross bridge formation requires Ca2+, when intracellular calcium levels are low, the muscle cell is relaxed because tropomyosin molecules physically block the myosin-binding sites on actin. As Ca2+ levels rise, the ions bind to regulatory sites on troponin. Two calcium ions must bind to a troponin, causing it to change shape and roll tropomyosin into the groove of the actin helix, away from the myosin binding sites. In short, the tropomyosin blockade is removed when sufficient calcium is present. • Once binding sites on actin are exposed, the events of the Cross Bridge Cycle occur in rapid succession • The cycle repeats and with each cycle, the myosin head takes another "step" by attaching to an actin site further along the thin filament. The thin filaments continue to slide as long as calcium and adequate ATP are present. • Myosin walks along the adjacent thin filaments during muscle shortening like a centipede. The thin filaments cannot slide backward as the cycle repeats again and again because some myosin heads (the "legs") are always in contact with actin (the "ground"). Contracting muscles routinely shorten by 30-35% of their total resting length, so each myosin cross bridge attaches and detaches many times during a single contraction. It is likely that only half of the myosin heads of a thick filament are pulling at the same instant. The others are randomly seeking their next binding site. • As soon as Ca2+ is released from the SR, the Ca2+ pumps of the SR begin to reclaim it from the cytosol. As Ca2+ levels drop, Ca2+ comes off of troponin, which again changes shape and pulls tropomyosin up to block actin's myosin-binding sites. The contraction ends, and the muscle fiber relaxes. When cross bridge cycling ends, the myosin heads remain in their upright high-energy configuration ready to bind actin when the muscle is stimulated to contract again. The cross bridge cycle series of events Note Except for the brief period following muscle cell excitation, calcium ion concentrations in the cytosol are kept almost undetectably low. When nerve impulses arrive in quick succession, intracellular Ca2 + levels soar due to successive "puffs" or bursts of Ca2+ released from the SR. In such cases, the muscle cells do not completely relax between successive stimuli and contraction is stronger and more sustained (within limits) until nervous stimulation ceases. Temporal summation and motor unit recruitment allow smooth, graded skeletal muscle contractions Before considering muscle contraction on the organ level, let's note two facts about muscle mechanics: 1. The principles governing contraction of a single muscle fiber and of a skeletal muscle consisting of a large number of fibers are pretty much the same. 2. The force exerted by a contracting muscle on an object is called Muscle Tension. The opposing force exerted on the muscle by the weight of the object to be moved is called the Load. *** The nerve-muscle functional unit called a Motor Unit The Motor Unit • Each muscle is served by at least one motor nerve, and each motor nerve contains axons (fibrous extensions) of up to hundreds of motor neurons. • As an axon enters a muscle, it branches into a number of endings, each of which forms a neuromuscular junction with a single muscle fiber. • A Motor Unit consists of one motor neuron and all the muscle fibers it innervates, or supplies. • When a motor neuron fires (transmits an action potential), all the muscle fibers it innervates contract. The number of muscle fibers per motor unit may be as high as several hundred or as few as four. • Muscles that exert fine control (such as those controlling the fingers and eyes) have small motor units. By contrast, large, weight-bearing muscles, whose movements are less precise (such as the hip muscles), have large motor units. • The muscle fibers in a single motor unit are not clustered together but are spread throughout the muscle. As a result, stimulation of a single motor unit causes a weak but uniform contraction of the muscle. A motor unit consists of one motor neuron and all the muscle fibers it innervates The Muscle Twitch • Muscle contraction is investigated in the laboratory using an isolated muscle. The muscle is attached to an apparatus that produces a Myogram, a recording of contractile activity consisting of one or more recorded lines called tracings. • Remember that muscles can contract without shortening (an isometric contraction) • The myograms (graphs) show the amount of tension a muscle develops when its length is held constant as it contracts. • In the laboratory, a muscle twitch is the response of a muscle to a single stimulation. The muscle fibers contract quickly and then relax. Every twitch myogram has three distinct phases: 1. Latent period. 2. Period of contraction. 3. Period of relaxation. The muscle twitch phases: Latent period: is the first few (ms) following stimulation when excitation-contraction coupling is occurring. During this period, cross bridges begin to cycle but muscle tension is not yet measurable so the myogram does not show a response. Period of contraction: cross bridges are active, from the onset to the peak of tension development, and the myogram tracing rises to a peak. This period lasts 10-100 ms. Period of relaxation: This final phase, lasting 10-100 ms, is due to pumping of Ca2+ back into the SR. Because the number of active cross bridges is declining, contractile force is declining. Muscle tension decreases to zero and the tracing returns to the baseline. **Notice that a muscle contracts faster than it relaxes. The differences between muscles reflect variations in enzymes and metabolic properties of the myofibrils. Graded Muscle Contractions • Muscle twitches-like those single, jerky contractions provoked in a laboratory-may result from certain neuromuscular problems, but this is not the way our muscles normally operate. Instead, healthy muscle contractions are relatively smooth and vary in strength as different demands are placed on them. These variations, needed for proper control of skeletal movement, are referred to as Graded Muscle Contractions. • In general, muscle contraction can be graded in two ways: 1. An increase in the frequency of stimulation causes temporal summation. The higher the frequency, the greater the strength of contraction of a given motor unit. 2. An increase in the strength of stimulation causes recruitment. The stronger the stimulation, the more motor units are activated, and the stronger the contraction. • In the body, the brain determines the strength of a muscle's contraction by changing (1) the rate of firing of action potentials along the axon of its motor neuron (Frequency) and (2) the number of its motor neurons that are activated (Strength). Muscle Response to Changes in Stimulus Frequency • The nervous system can achieve greater muscular force by increasing the firing rate of motor neurons. For example, if two identical stimuli (electrical shocks or nerve impulses) are delivered to a muscle in rapid succession, the second twitch will be stronger than the first. • On a myogram the second twitch will appear to ride on the shoulders of the first. • This phenomenon is called Temporal, or Wave-Summation. It occurs because the second contraction begins before the muscle has completely relaxed. • The second contraction is greater than the first because the muscle is already partially contracted and because even more calcium is squirted into the cytosol. • In other words, the contractions are added together. (However, the refractory period is always honored. So if a second stimulus arrives before repolarization is complete, no wave summation occurs) If the muscle is stimulated at an increasingly faster rate: 1. The relaxation time between twitches becomes shorter and shorter. 2. The concentration of Ca2 + in the cytosol rises higher and higher. 3. The degree of wave summation becomes greater and greater, progressing to a sustained but quivering contraction referred to as unfused or incomplete tetanus 4. Finally, as the stimulation frequency continues to increase, muscle tension increases until it reaches maximal tension. At this point all evidence of muscle relaxation disappears and the contractions fuse into a smooth, sustained contraction plateau called fused or complete tetanus. **In the real world, physiological mechanisms prevent fused tetanus, so it rarely if ever occurs. Temporal summation contributes to contractile force, but its primary function is to produce smooth, continuous muscle contractions by rapidly stimulating a specific number of muscle cells. Muscle Response to Changes in Stimulus Strength: Recruitment • Also called Multiple Motor Unit Summation, controls the force of contraction more precisely. In the laboratory, recruitment is achieved by delivering stimuli of increasing voltage, calling more and more muscle fibers into play: 1-Stimuli that produce no observable contractions are subthreshold stimuli. 2- The stimulus at which the first observable contraction occurs is called the threshold stimulus . Beyond this point, the muscle contracts more vigorously as the stimulus strength increases. 3- The maximal stimulus is the strongest stimulus that increases contractile force. It represents the point at which all the muscle's motor units are recruited. In the laboratory, increasing the stimulus intensity beyond the maximal stimulus does not produce a stronger contraction. • The recruitment process is not random. Instead it is dictated by the size principle. In any muscle: 1- The motor units with the smallest muscle fibers are activated first because they are controlled by the smallest, most highly excitable motor neurons. 2- As motor units with larger and larger muscle fibers begin to be excited, contractile strength increases. 3- The largest motor units, containing large, coarse muscle fibers, are controlled by the largest, least excitable (highest threshold) neurons and are activated only when the most powerful contraction is necessary . Muscle Response to Changes in Stimulus Strength: Recruitment. Why is the size principle important? • It allows the increases in force during weak contractions (for example, those that maintain posture or slow movements) to occur in small steps, whereas gradations in muscle force are progressively greater when large amounts of force are needed for vigorous activities such as jumping or running. • The size principle explains how the same hand that lightly pats your cheek can deliver a stinging slap at the volleyball during a match. • Although all the motor units of a muscle may be recruited simultaneously to produce an exceptionally strong contraction, motor units are more commonly activated Asynchronously. • At a given instant, some are contracting while others are resting and recovering. This technique helps prolong a strong contraction by preventing or delaying fatigue. • It also explains how weak contractions promoted by infrequent stimuli can remain smooth. Muscle Tone • Skeletal muscles are described as voluntary, but even relaxed muscles are almost always slightly contracted, a phenomenon called Muscle Tone. • Muscle tone is due to spinal reflexes that activate first one group of motor units and then another in response to activated stretch receptors in the muscles. • Muscle tone does not produce active movements, but it keeps the muscles firm, healthy, and ready to respond to stimulation. • Skeletal muscle tone also helps stabilize joints and maintain posture. Isotonic and Isometric Contractions There are two main categories of contractions: Isotonic and Isometric, depending on whether a muscle changes length or not. Muscles change length in isotonic, but not isometric, contractions. Isotonic Contractions: • If the muscle tension developed overcomes the load and muscle shortening occurs, the contraction is an isotonic contraction. • Once sufficient tension has developed to move the load, the tension remains relatively constant through the rest of the contractile period. • Isotonic contractions come in two "flavors"-concentric and eccentric. • Concentric contractions are those in which the muscle shortens and does work, such as picking up a book or kicking a ball. Concentric contractions are probably more familiar, but eccentric contractions, in which the muscle generates force as it lengthens, are equally important for coordination and purposeful movements. • Eccentric contractions occur in your anterior thigh muscles. Are about 50% more forceful than concentric ones at the same load and more often cause delayed-onset muscle soreness. The muscle stretching that occurs during eccentric contractions causes microtrauma in the muscles that results in soreness. • Biceps curls provide a simple example of how concentric and eccentric contractions work together. When flex the elbow to draw a weight toward the shoulder, Biceps muscle in the arm is contracting concentrically. When straighten the arm to return the weight to the bench, the isotonic contraction of your biceps is eccentric. • Basically, Eccentric Contractions put the body in position to contract concentrically. Isometric Contractions • A contracting muscle does not always shorten and move a load. • If muscle tension develops but the load is not moved, the contraction is an isometric contraction • In isometric contractions, tension may build to the muscle's peak tension-producing capacity, but the muscle neither shortens nor lengthens, because the load is greater than the force (tension) the muscle is able to develop. * Think of trying to lift a piano single-handedly. • Muscles contract isometrically when they act primarily to maintain upright posture or to hold joints stationary while movements occur at other joints. • Electrochemical and mechanical events occurring within a muscle are identical in both isotonic and isometric contractions. However, the results are different. ln isotonic contractions, the thin filaments slide. In isometric contractions, the cross bridges generate force but do not move the thin filaments, so there is no change in the banding pattern from that of the resting state. • You could say that they are "spinning their wheels" on the same actin binding sites. ATP for muscle contraction is produced aerobically or anaerobically Providing Energy for Contraction • As a muscle contracts, ATP supplies the energy to move and detach cross bridges, operate the calcium pump in the SR, and operate the Na+-K+ pump in the plasma membrane. • Surprisingly, muscles store very limited reserves of ATP 4 to 6 seconds' worth at most, just enough to get you going. • Because ATP is the only energy source used directly for contractile activities, it must be regenerated as fast as it is broken down if contraction is to continue. • Fortunately, after ATP is hydrolyzed to ADP and inorganic phosphate in muscle fibers, it is regenerated within a fraction of a second by one or more of the three pathways: (a) Direct phosphorylation of ADP by creatine phosphate, (b) Anaerobic glycolysis, which converts glucose to lactic acid, and (c) Aerobic respiration. All body cells use glycolysis and aerobic respiration to produce ATP. Direct Phosphorylation of ADP by Creatine Phosphate • As we begin to exercise vigorously, the demand for ATP soars and the ATP stored in working muscles is consumed within a few twitches. Then creatine phosphate (CP), a unique high-energy molecule stored in muscles, is tapped to regenerate ATP while other metabolic pathways adjust to the sudden high demand for ATP. Coupling CP with ADP transfers energy and a phosphate group from CP to ADP to form ATP ahnost instantly: Creatine kinase Creatine phosphate + ADP Creatine + ATP • Muscle cells store two to three times more CP than ATP. The CP reaction with ADP, catalyzed by the enzyme creatine kinase, is so efficient that the amount of ATP in muscle cells changes very little during the initial period of contraction. Together, stored ATP and CP provide for maximum muscle power for about 15 seconds-long enough to energize a 100- meter dash. • The coupled reaction is readily reversible, and to keep CP available, CP reserves are replenished during periods of rest or inactivity. Anaerobic Pathway: Glycolysis and Lactic Acid Formation • As stored ATP and CP are exhausted, more ATP is generated by breaking down (catabolizing) glucose obtained from the blood or glycogen stored in the muscle. The initial phase of glucose breakdown is glycolysis. • This pathway occurs in both the presence and the absence of oxygen, but because it does not use oxygen, it is an anaerobic pathway. • During glycolysis, glucose is broken down to two pyruvic acid molecules, releasing enough energy to form small amounts of ATP (2 ATP per glucose). When sufficient oxygen is present, the pyruvic acid produced during glycolysis enters the mitochondria, producing still more ATP in the oxygen-using pathway called aerobic respiration. • When blood flow and oxygen delivery are impaired during vigorous muscle contraction, most of the pyruvic acid is converted into lactic acid, and the overall process is referred to as anaerobic glycolysis. • Oxygen delivery is impaired because bulging muscles compress the blood vessels within them. This happens when contractile activity reaches about 70% of the maximum possible. • Lactic acid is the end product of glucose metabolism during anaerobic glycolysis. Most of the lactic acid diffuses out of the muscles into the bloodstream. Subsequently, the liver, heart, or kidney cells pick up the lactic acid and use it as an energy source. Anaerobic Pathway: Glycolysis and Lactic Acid Formation- Cont. • Additionally, liver cells can reconvert it to pyruvic acid or glucose and release it back into the bloodstream for muscle use or convert it to glycogen for storage. • The anaerobic pathway is inefficient but fast. It harvests only about 5% as much ATP from each glucose molecule as the aerobic pathway, but it produces ATP about 2 and half times faster. For this reason, even when large amounts of ATP are needed for moderate periods (30-40 seconds) of strenuous muscle activity, glycolysis can provide most of this ATP. • Together, stored ATP and CP and the glycolysis-lactic acid pathway can support strenuous muscle activity for nearly a minute. Although anaerobic glycolysis readily fuels spurts of vigorous exercise, it has shortcomings. • Huge amounts of glucose are used to produce relatively small harvests of ATP, and the accumulating lactic acid is partially responsible for muscle soreness during intense exercise. Aerobic Respiration • During rest and light to moderate exercise, even if prolonged, 95% of the ATP used for muscle activity comes from aerobic respiration. Aerobic respiration requires oxygen and mitochondria, and involves a sequence of chemical reactions that break the bonds of fuel molecules and release energy to make ATP. • Aerobic respiration begins with glycolysis and is followed by reactions that take place in the mitochondria. It breaks down glucose entirely to water and carbon dioxide, and generates large amounts of ATP. Glucose + oxygen carbon dioxide + water + ATP • The carbon dioxide released diffuses out of the muscle tissue into the blood, to be removed from the body by the lungs. As exercise begins, muscle glycogen provides most of the fuel. Shortly thereafter, blood-borne glucose, pyruvic acid from glycolysis, and free fatty acids are the major sources of fuels. After about 30 minutes, fatty acids become the major energy fuels. Aerobic respiration provides a high yield of ATP (about 32 ATP per glucose), but it is slow because of its many steps and it requires continuous delivery of oxygen and nutrient fuels to keep it going Which pathways predominate during exercise? As long as a muscle cell has enough oxygen, it will form ATP by the aerobic pathway. • When ATP demands are within the capacity of the aerobic pathway, light to moderate muscular activity can continue for several hours in well-conditioned individuals. • However, when exercise demands begin to exceed the ability of the muscle cells to carry out the necessary reactions quickly enough, anaerobic pathways begin to contribute more and more of the total ATP generated. • The length of time a muscle can continue to contract using aerobic pathways is called Aerobic Endurance, and the point at which muscle metabolism converts to anaerobic glycolysis is called Anaerobic Threshold. • Activities that require a surge of power but last only a few seconds, such as weight lifting, diving, and sprinting, rely entirely on ATP and CP stores. The slightly longer bursts of activity in tennis, soccer, and a 100-meter swim appear to be fueled almost entirely by anaerobic glycolysis. • Prolonged activities such as marathon runs and bicycle touring, where endurance rather than power is the goal, depend mainly on aerobic respiration using both glucose and fatty acids as fuels. • Levels of CP and ATP don't change much during prolonged exercise because ATP is generated at the same rate as it is used- a "pay as you go" system. • Compared to anaerobic energy production, aerobic generation of ATP is relatively slow, but the ATP harvest is enormous. Energy Systems Used du ring Exercise Muscle Fatigue Muscle fatigue is a state of physiological inability to contract even though the muscle is still receiving stimuli. You might think that running out of ATP is the critical event that causes muscle fatigue. In fact, ATP levels inside muscle cells do drop, but muscle fatigue serves to prevent complete depletion of ATP in muscle, which would result in death of muscle cells and rigor mortis. The mechanism of muscle fatigue is complex. Although it is not fully understood, it involves alterations in excitation-contraction coupling. The following chemical changes may be involved: 1. Ionic imbalances: Several ionic imbalances contribute to muscle fatigue. As action potentials are transmitted, potassium is lost from the muscle cells to the fluids of the T tubules and Na+ is gained. These ionic changes disturb the membrane potential of the muscle cells. They also reduce the size of the action potential, which reduces the movement of the voltage sensitive proteins in the T tubules and so reduces the amount of Ca2+ released from the SR. 2. Increased inorganic phosphate: Pi from CP and ATP breakdown may interfere with calcium release from the SR. It may also interfere with the release of Pi from myosin and thus hamper myosin's power strokes. 3. Decreased ATP and increased magnesium (Mg2+ ): ATP normally binds Mg2 + in the cell, so as ATP levels drop, Mg2+ levels rise. Both low ATP and high Mg2+ act on the voltage-sensitive proteins in the T tubule to decrease Ca2+ release from the SR. 4. Decreased glycogen: is highly correlated with muscle fatigue. Lactic acid has long been assumed to be a major cause of fatigue, and excessive intracellular accumulation of lactic acid raises the concentration of H+ and alters contractile proteins. Although lactic acid and pH both contribute to the sensation of pain during intense exercise, neither seem to be directly involved in muscle fatigue. In general, intense exercise of short duration produces fatigue rapidly, but recovery is also rapid. In contrast, the slow developing- fatigue of prolonged low-intensity exercise may require hours to days for complete recovery. Excess Postexercise Oxygen Consumption (EPOC): • Whether or not fatigue occurs, vigorous exercise alters a muscle's chemistry dramatically. For a muscle to return to its preexercise state, the following must occur: 1. Its oxygen reserves (stored in myoglobin) must be replenished. 2. The accumulated lactic acid must be reconverted to pyruvic acid. 3. Glycogen stores must be replaced. 4. ATP and creatine phosphate reserves must be resynthesized. • The use of these muscle stores during anaerobic exercise simply defers when the oxygen is consumed, because replacing them requires oxygen uptake and aerobic metabolism after exercise ends. • Additionally, the liver must convert any lactic acid persisting in blood to glucose or glycogen. Once exercise stops, the repayment process begins. • The extra amount of oxygen that the body must take in for these restorative processes is called the Excess Postexercise Oxygen Consumption (EPOC), formerly called the Oxygen Debt. • EPOC represents the difference between the amount of oxygen needed for totally aerobic muscle activity and the amount actually used. All anaerobic sources of ATP used during muscle activity contribute to EPOC. The force, velocity, and duration of skeletal muscle contractions are determined by a variety of factors The force of muscle contraction depends on the number of myosin cross bridges that are attached to actin. This in turn is affected by four factors: 1. Frequency of stimulation. When a muscle is stimulated more frequently, contractions are summed (temporal summation and tetany) The higher the frequency of muscle stimulation, the greater the force the muscle exerts. 2. Number of muscle fibers recruited. The more motor units recruited, the greater the force. 3. Size of muscle fibers. The bulkier the muscle and the greater the cross-sectional area, the more tension it can develop. The large fibers of large motor units produce the most powerful movements. Regular resistance exercise increases muscle force by causing muscle cells to hypertrophy (increase in size). 4. Degree of muscle stretch. If a muscle is stretched to various lengths and maximally stimulated, the tension the muscle can generate varies with length. The amount of tension a muscle can generate during an isometric contraction at various lengthLength- tension relationship. The ideal length on this curve occurs when the muscle is close to its resting length and the thin and thick filaments overlap optimally, because this permits sliding along nearly the entire length of the thin filaments. If a muscle is stretched so much that the filaments do not overlap, the myosin heads have nothing to attach to and cannot generate tension. On the other hand, if the sarcomeres are so compressed that the thin filaments interfere with one another, little or no further shortening can occur. Factors that increase the force of skeletal muscle contraction. Velocity and Duration of Contraction Muscles Vary in how fast they can contract and how long they can continue to contract before they fatigue. These characteristics are influenced by Muscle Fiber Type, Load, and Recruitment. Muscle Fiber Type: There are several ways of classifying muscle fibers, but learning about these classes will be easier if you pay attention to just two functional characteristics: ▪ Speed of contraction. On the basis of speed (velocity) of fiber shortening, there are slow fibers and fast fibers. The difference reflects how fast their myosin ATPases split ATP, and the pattern of electrical activity of their motor neurons. Contraction duration also varies with fiber type and depends on how quickly Ca2+ moves from the cytosol into the SR. ▪ Major pathways for forming ATP. The cells that rely mostly on the oxygen-using aerobic pathways for ATP generation are Oxidative Fibers. Those that rely more on anaerobic glycolysis and creatine phosphate are glycolytic fibers. ** Using these two criteria, we can classify skeletal muscle cells as: Slow Oxidative Fibers, Fast Oxidative Fibers, Fast Glycolytic Fibers Slow Oxidative Fiber • Contracts slowly because its myosin ATPases are slow (a criterion) • Depends on oxygen delivery and aerobic pathways (its major pathways for forming ATP give it high oxidative capacity-a criterion) • Resists fatigue and has high endurance (typical of fibers that depend on aerobic metabolism) • Is thin (a large amount of cytoplasm impedes diffusion of 02 and nutrients from the blood) • Has relatively little power (a thin cell can contain only a limited number of myofibrils) • Has many mitochondria (actual sites of oxygen use) • Has a rich capillary supply • Is red (its color stems from an abundant supply of myoglobin, muscle's oxygen-binding pigment) Fast Glycolytic Fiber Fast Oxidative Fibers • Contracts rapidly due to the activity of• They have many characteristics fast myosin ATPases intermediate between the other two types (glycogen stores and • Uses little oxygen power, for example). • Depends on glycogen reserves for fuel• rather than on blood-delivered nutrients • Tires quickly because glycogen reserves are short-lived, making it a fatigable fiber. Like fast glycolytic fibers, they contract quickly, but like slow oxidative fibers, they are oxygen dependent and have a rich supply of myoglobin and capillaries. • Has a relatively large diameter, • Some muscles have a indicating both the plentiful predominance of one fiber type, myofilaments that allow it to contract but most contain a mixture of powerfully before it "tires out" and its fiber types, which gives them a lack of dependence on continuous range of contractile speeds and oxygen and nutrient diffusion from the fatigue resistance. blood • Has few mitochondria, little • But, all muscle fibers in a myoglobin, and few capillaries (making particular motor unit are of the it white) same type. Load and Recruitment • Because muscles are attached to bones, they are always pitted against some resistance, or Load, when they contract. • They contract fastest when there is no added load on them. A greater load results in a longer latent period, slower shortening, and a briefer duration of shortening. • The more motor units that are contracting, the faster and more prolonged the contraction. The amount of work a muscle does is reflected in changes in the muscle itself. When used actively or strenuously, muscles may become larger or stronger, or more efficient and fatigue resistant. • Exercise gains are based on the overload principle. Forcing a muscle to work hard increases its strength and endurance. • As muscles adapt to greater demand, they must be overloaded to produce further gains. Inactivity, on the other hand, always leads to muscle weakness and atrophy. Aerobic (Endurance) • Aerobic Exercise such as swimming, running, fast walking, and biking results in several recognizable changes in skeletal muscles: 1. The number of capillaries surrounding the muscle fibers increases. 2. The number of mitochondria within the muscle fibers also increases. 3. The fibers synthesize more myoglobin. • These changes occur in all fiber types, but are most dramatic in slow oxidative fibers, which depend primarily on aerobic pathways. The changes result in more efficient muscle metabolism and in greater endurance, strength, and resistance to fatigue. • Regular endurance exercise may convert fast glycolytic fibers into fast oxidative fibers. Resistance Exercise • The moderately weak but sustained muscle activity required for endurance exercise does not promote significant skeletal muscle hypertrophy, even though the exercise may go on for hours. • Muscle hypertrophy-think of the bulging biceps of a professional weight lifter-results mainly from high-intensity resistance exercise (typically under