BIOL2012SEF Musculoskeletal System PDF

BIOL2012SEF Musculoskeletal System Dr Emily Wong 1 Action Potential Musculoskeletal System 2 Neuron Most neurons consist of 3 parts Dendrite Cell body Axon 3 Structure of a Neuron 4 Synapses Synapses can use both chemical and electrical stimuli to pass information. Synapses can also be inhibitory or...

BIOL2012SEF Musculoskeletal System Dr Emily Wong 1 Action Potential Musculoskeletal System 2 Neuron Most neurons consist of 3 parts Dendrite Cell body Axon 3 Structure of a Neuron 4 Synapses Synapses can use both chemical and electrical stimuli to pass information. Synapses can also be inhibitory or excitatory depending on the signal/ neurotransmitter being transmitted. 5 5 Basic Principles of Electricity 6 Membrane Potentials Different cells have different resting membrane potentials. Neurons have a resting membrane potential generally in the range of –40 to –90 mV. Changes in potential are due to movement of ions. 7 8 Membrane Potentials Different cells have different resting membrane potentials. Neurons have a resting membrane potential generally in the range of –40 to –90 mV. Changes in potential are due to movement of ions. 9 10 Terminology When talking about action potentials and graded potentials we use these terms: depolarization, repolarization, hyperpolarization. These terms are all relative to the resting membrane potential (RMP). Depolarization is the potential moving from RMP to less negative values. Repolarization is the potential moving back to the RMP. Hyperpolarization is the potential moving away from the RMP in a more negative direction. 11 12 Action Potentials Action potentials are generally very rapid (as brief as 1–4 milliseconds) and may repeat at frequencies of several hundred per second. The ability to generate action potentials is known as excitability. This ability is possessed by neurons, muscle cells and some other types of cells. An action potential is a large change in membrane potential and is an “all or none” response. 13 Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in presentation mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Slide Show mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 14 Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in presentation mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Slide Show mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 15 Bone Primary organs of Skeletal System Connective tissues Compact bone: (also called dense or cortical bone) Relatively dense connective bone tissue Appears white, smooth and solid ~80% of total bone mass Spongy bone: (also called cancellous or trabecular bone) Located internal to compact bone Porous ~20% of total bone mass 16 Connective tissues Cartilage: semi-rigid connective tissue that is more flexible than bone Hyaline cartilage: Articular cartilage: Covers the end of bones Epiphyseal cartilage: cartilage within the growth plates Fibrocartilage: Weight-bearing cartilage Intervertebral discs Cartilage pads of knee joints (menisci) 17 Connective tissues Ligaments: anchor bone to bone Tendons: connect muscle to bone 18 Functions of Skeletal System Support and Protection 2. Movement 3. Hemopoiesis 4. Storage of mineral and energy reserves 1. 19 1. Support and Protection Bones can provide structural support and serve as a framework for the entire body protect delicate organs and tissues from injury and trauma Rib cage protects heart and lungs Cranial bones enclose and protect the brain 20 2. Movement When muscles attached to the bones of the skeleton contract, they exert a pull on the skeleton that functions as a system of levers  M: motion 21 3. Hemopoiesis Blood cell production Occurs in red bone marrow Erythropoiesis: RBC formation Thrombopoiesis: platelet formation Leukopoiesis: immune cells formation 22 23 4. Storage of mineral and energy reserves Storage of calcium and phosphate 24 Muscle Physiology Muscle is classified as Skeletal muscle Smooth muscle Cardiac muscle Each type of muscle has specific characteristics and functions. 25 Characteristics of a Skeletal Muscle Fiber A skeletal muscle cell (“fiber”) has several defining characteristics: 1. It is multinucleated. 2. It contains many mitochondria. 3. It has special structures called Transverse tubules (T tubules). 4. It has myofibrils and sarcomeres. 5. It has specific terms for some of the intracellular structures: Sarcolemma = Plasma membrane Sarcoplasm = Cytoplasm Sarcoplasmic reticulum = Smooth ER 26 Myofibrils Myofibrils are the structures that give skeletal and cardiac muscle their characteristic striated appearance. They are orderly arrangements of thick and thin filaments: – Actin (thin) – Myosin (thick) 27 Structure of Skeletal Muscle 28 Structure of Sarcomere 29 Molecular Mechanisms of Skeletal Muscle Contraction The term contraction does not necessarily mean “shortening.” It simply refers to activation of the force-generating sites within muscle fibers—the cross-bridges. For example, holding a dumbbell at a constant position requires muscle contraction, but not muscle shortening. 30 Sliding Filament Mechanism In this model of contraction force generation produces shortening of a skeletal muscle fiber, the overlapping thick and thin filaments in each sarcomere move past each other, propelled by movements of the cross-bridges. The ability of a muscle fiber to generate force and movement depends on the interaction of the contractile proteins actin and myosin. 31 Sliding Filament Mechanism 32 Thin Filaments and Associated Proteins Actin: Contractile protein Each G actin has a binding site for myosin. Think of pearls strung together on a string and then the strands of pearls are twisted together. Tropomyosin: Regulatory protein Overlaps binding sites on actin for myosin and inhibits interaction when in the relaxed state. 33 Thin Filaments and Associated Proteins Troponin: Regulatory protein Forms a complex with the other proteins of the thin filament (actin and tropomyosin). Troponin binds Ca2+ reversibly and once bound changes conformation to pull tropomyosin away from the myosin interaction sites. Ca2+ binding to troponin regulates skeletal muscle contraction because it moves the tropomyosin away and allows myosin to interact with the actin. 34 The Cross-bridge Cycle Functions of ATP in Skeletal Muscle Contraction 36 Roles of Troponin, Tropomyosin, and Ca2+ in Contraction 37 Action Potentials and Contraction 38 Mechanics of Single-fiber Contractions A muscle fiber generates force called tension in order to oppose a force called the load, which is exerted on the muscle by an object. The mechanical response of a muscle fiber to a single action potential is known as a twitch. 39 The Phases of a Twitch Contraction There are 3 major phases to a twitch contraction: 1.Latent Period This is the period of time from the action potential to the onset of contraction. The short time delay (e.g. 1-2 msec) is due to the excitation-contraction coupling. 2.Contraction Phase This is the time that tension is developing due to the cross-bridge cycling. 3.Relaxation Phase 40 This is the time that the tension is decreasing (i.e., relaxing) and is longer than the contraction phase. This is due to the amount of time it takes to get all the Ca2+ sequestered. Twitch Contractions 41 Isometric and Isotonic Twitches: Isometric twitches generate tension but do not shorten the muscle (load is greater than the force generated by the muscle…i.e., postural muscles). Isotonic twitches do shorten the muscle. 42 Frequency-tension Relationship Because a single action potential in a skeletal muscle fiber lasts only 1 to 2 ms but the twitch may last for 100 ms, it is possible for a second action potential to be initiated during the period of mechanical activity. When a stimulus is applied before a fiber has completely relaxed from a twitch, it induces a contractile response with a peak tension greater than that produced in a single twitch (Figure 9.19, S3 and S4). The increase in muscle tension from successive action potentials occurring during the phase of mechanical activity is known as summation. A maintained contraction in response to repetitive stimulation is known as a tetanus (tetanic contraction). 43 Frequency-tension Relationship 44 Skeletal Muscle Energy Metabolism As we have seen, ATP performs three functions directly related to muscle fiber contraction and relaxation. There are three ways a muscle fiber can form ATP: 1. Phosphorylation of ADP by creatine phosphate 2. Oxidative phosphorylation of ADP in the mitochondria 3. Phosphorylation of ADP by the glycolytic pathway in the cytosol 45 Skeletal Muscle Energy Metabolism 46 Muscle Fatigue When a skeletal muscle fiber is repeatedly stimulated, the tension the fiber develops eventually decreases even though the stimulation continues. This decline in muscle tension as a result of previous contractile activity is known as muscle fatigue. Additional characteristics of fatigued muscle are a decreased shortening velocity and a slower rate of relaxation. The onset of fatigue and its rate of development depend on the type of skeletal muscle fiber that is active, the intensity and duration of contractile activity, and the degree of an individual’s fitness. 47 Muscle Fatigue Causes Many factors can contribute to the fatigue of skeletal muscle. Acute fatigue from high-intensity, short-duration exercise is thought to involve: decrease in ATP concentration. increase in concentrations of ADP, Pi, Mg2+ , H+ and oxygen free radicals. These have been shown to: decrease the rate of Ca2+ release, reuptake and storage by the endoplasmic reticulum. decrease the sensitivity of the thin filament proteins to activation by Ca2+ release. directly inhibit the binding and power-stroke motion of the myosin crossbridges. Each of these has been shown to be important under experimental conditions but muscle fatigue is still not well understood. 48 Muscle Fatigue Causes Central Command Fatigue Another type of fatigue quite different from muscle fatigue occurs when the appropriate regions of the cerebral cortex fail to send excitatory signals to the motor neurons. This may cause a person to stop exercising even though the muscles are not fatigued. An athlete’s performance depends not only on the physical state of the appropriate muscles but also upon the “will to win”—that is, the ability to initiate central commands to muscles during a period of increasingly distressful sensations. 49 Muscle Fatigue 50 Muscle Movements 51 Muscle Movements 52 Skeletal Muscle Disorders A number of conditions and diseases can affect the contraction of skeletal muscle. Many of them are caused by defects in the parts of the nervous system that control contraction of the muscle fibers rather than by defects in the muscle fibers themselves. 53 Muscle Cramps Involuntary tetanic contraction of skeletal muscles produces muscle cramps. During cramping, action potentials fire at abnormally high rates, a much greater rate than occurs during maximal voluntary contraction. The specific cause of this high activity is uncertain, but it is probably related to electrolyte imbalances in the extracellular fluid surrounding both the muscle and nerve fibers. These imbalances may arise from overexercise or persistent dehydration, and they can directly induce action potentials in motor neurons and muscle fibers. Another theory is that chemical imbalances within the muscle stimulate sensory receptors in the muscle, and the motor neurons to the area are activated by reflex when those signals reach the spinal cord. 54 Hypocalcemic Tetany Hypocalcemic tetany is the involuntary tetanic contraction of skeletal muscles that occurs when the extracellular Ca2+ concentration falls to about 40 percent of its normal value. This may seem surprising, because we have seen that Ca2+ is required for excitation-contraction coupling. However, recall that this Ca2+ is sarcoplasmic reticulum Ca2+, not extracellular Ca2+. The effect of changes in extracellular Ca2+ is exerted not on the sarcoplasmic reticulum Ca2+, but directly on the plasma membrane. Low extracellular Ca2+ (hypocalcemia) increases the opening of Na+ channels in excitable membranes, leading to membrane depolarization and the spontaneous firing of action potentials. 55 Structure of Smooth Muscle Each smooth muscle cell is spindle-shaped, with a diameter between 2 and 10 µm, and length ranging from 50 to 400 µm. They are much smaller than skeletal muscle fibers, which are 10 to 100 µm wide and can be tens of centimeters long. Smooth muscle cells (SMC) have a single nucleus and have the capacity to divide throughout the life of an individual. SMCs have thick myosin-containing filaments and thin actin-containing filaments, and tropomyosin but NO troponin. The thin filaments are anchored either to the plasma membrane or to cytoplasmic structures known as dense bodies. 56 Structure of Smooth Muscle The thick and thin filaments are not organized into myofibrils, and there are NO sarcomeres, which accounts for the absence of a banding pattern. Smooth muscle contraction occurs by a sliding-filament mechanism. Smooth muscles surround hollow structures and organs that undergo changes in volume with accompanying changes in the lengths of the smooth muscle fibers in their walls. 57 Structure of Smooth Muscle 58 Smooth Muscle Contraction and its Control Cross-Bridge Activation: Cross-bridge cycling in smooth muscle is controlled by a Ca2+regulated enzyme that phosphorylates myosin. Only the phosphorylated form of smooth muscle myosin can bind to actin and undergo cross-bridge cycling. This is done by myosin light chain kinase (MLCK). To relax a contracted smooth muscle, myosin must be dephosphorylated because dephosphorylated myosin is unable to bind to actin. This dephosphorylation is mediated by the enzyme myosin light-chain phosphatase (MLCP). 59 Sources of Cytosolic Ca2+ Two sources of Ca2+ contribute to the rise in cytosolic Ca2+ that initiates smooth muscle contraction: The sarcoplasmic reticulum 2. Extracellular Ca2+ entering the cell through plasmamembrane Ca2+ channels 1. To relax, the Ca2+ has to be removed either to the SR or back to the extracellular fluid. 60 Membrane Activation Smooth muscle responses can be graded. Input to smooth muscle can be either excitatory or inhibitory. 61 Cross-bridge Activation 62 Smooth Muscle Contraction and its Control 63 Nerves and Hormones The contractile activity of smooth muscles is influenced by neurotransmitters released by autonomic neuron endings. Unlike skeletal muscle fibers, smooth muscle cells do not have a specialized motor end-plate region. They have swollen regions known as varicosities. Each varicosity contains many vesicles filled with neurotransmitter, some of which are released when an action potential passes the varicosity. Varicosities from a single axon may be located along several muscle cells, and a single muscle cell may be located near varicosities belonging to postganglionic fibers of both sympathetic and parasympathetic neurons. Therefore, a number of smooth muscle cells are influenced by the neurotransmitters released by a single neuron, and a single smooth muscle cell may be influenced by neurotransmitters from more than one neuron. 64 Nerves and Hormones Whereas some neurotransmitters enhance contractile activity, others decrease contractile activity. A given neurotransmitter may produce opposite effects in different smooth muscle tissues. For example, norepinephrine, the neurotransmitter released from most postganglionic sympathetic neurons, enhances contraction of most vascular smooth muscle by acting on alpha-adrenergic receptors, but produces relaxation of airway (bronchiolar) smooth muscle by acting on beta-2 adrenergic receptors. Thus, the type of response (excitatory or inhibitory) depends not on the chemical messenger per se, but on the receptors the chemical messenger binds to in the membrane and on the intracellular signaling mechanisms those receptors activate. 65 Local Factors Local factors, including paracrine signals, acidity, O2 and CO2 levels, osmolarity, and the ion composition of the extracellular fluid, can also alter smooth muscle tension. Responses to local factors provide a means for altering smooth muscle contraction in response to changes in the muscle’s immediate internal environment, independent of long-distance signals from nerves and hormones. Many of these local factors induce smooth muscle relaxation. Nitric oxide (NO) which produces smooth muscle relaxation. NO acts in a paracrine manner. Some smooth muscles can also respond by contracting when they are stretched. Stretching opens mechanosensitive ion channels, leading to membrane depolarization. The resulting contraction opposes the forces acting to stretch the muscle. 66 Spontaneous Electrical Activity Some types of smooth muscle cells generate action potentials spontaneously in the absence of any neural or hormonal input. The membrane potential change occurring during the spontaneous depolarization to threshold is known as a pacemaker potential. Other smooth muscle pacemaker cells have a slightly different pattern of activity. The membrane potential drifts up and down due to regular variation in ion flux across the membrane. These periodic fluctuations are called slow waves. Pacemaker cells are found throughout the gastrointestinal tract, and thus gut smooth muscle tends to contract rhythmically even in the absence of neural input. Some cardiac muscle fibers and a few neurons in the central nervous system also have pacemaker potentials and can spontaneously generate action potentials in the absence of external stimuli. 67 Souces of Cytosolic Calcium Calcium that initiates smooth muscle contraction comes from both the sarcoplasmic reticulum and from the extracellular fluid entering through plasma-membrane channels. 68 Membrane Activation 69 Factors Affecting Smooth Muscle Contraction 70 Types of Smooth Muscle Single-unit smooth muscles respond to stimuli as a single unit because cells are connected by gap junctions. Multi-unit smooth muscles contain cells that respond to stimuli independently and they contain few gap junctions. 71 Cardiac Muscle Cardiac muscle cells have one to two nuclei that are centrally located. They are striated and use the sliding filament mechanism to contract. They are branching cells with intercalated discs with desmosomes and gap junctions. The gap junctions are critical to the heart’s ability to be electrically coupled. The nodal cells have the ability to stimulate their own action potentials. This is called automaticity or autorhythmicity. The absolute refractory period is about 250 ms. This prevents tetanic contractions which would interfere with the heart’s ability to pump. 72 Cellular Structure of Cardiac Muscle 73 Excitation-Contraction Coupling in Cardiac Muscle 74 Skeletal vs Cardiac Muscle 75 Characteristics of Muscle Cells 76