Lecture 5&6 W25 Muscular System PDF

Lecture 5 MUSCULAR SYSTEM, PART 1 learning objectives for this lecture: a. understand structure of skeletal muscles b. understand the molecular basis of muscle contraction c. understand neural control of muscle contraction Three types of vertebrate muscle: Skeletal: voluntary movement (walking...

Lecture 5 MUSCULAR SYSTEM, PART 1 learning objectives for this lecture: a. understand structure of skeletal muscles b. understand the molecular basis of muscle contraction c. understand neural control of muscle contraction Three types of vertebrate muscle: Skeletal: voluntary movement (walking, breathing, etc.). Most skeletal muscles are connected to bones by tendons Cardiac: beating of heart Smooth: involuntary, controls blood flow, movement of food through digestive tract, and many other things this shows shows a microscopic image of skeletal muscle. skeletal muscle fibers are highly unusual cells Very big and long. Skeletal muscle fibers can be up to 0.1 mm in diameter and up to 30 cm long. Each muscle fiber has multiple nuclei. The shape and size of these cells in central to their function These huge cells develop by the fusion of smaller cells into long fibers (next slide) one cell (fiber) stem cell  skeletal muscles move our bodies muscles generate the force to move our bodies by shortening  to understand how a muscle generates force we need to look at the cellular and molecular structure of muscles A skeletal muscle consists of a bundle of long fibers, each a single cell, running along the length of the muscle (muscle fiber) Each muscle fiber (cell) is itself a bundle of smaller subcellular myofibrils arranged longitudinally within the cell The myofibrils are bundles of organized contractile protein molecules called sarcomeres. These generate the contractile force. Molecular Basis of Fiber Contraction Muscle fiber (cell) contraction relies on the interaction between thin filaments, composed mainly of the proteins actin, and thick filaments, staggered arrays of myosin  force is generated when the sarcomeres contract actin filaments (thin filaments) are anchored to the Z line the thick filaments made of myosin pull on the actin filaments to shorten the z lines = z bands=z disk distance between the Just different names for the Z lines same thing  HOW DOES THE MYOSIN PULL THE Z LINES TOGETER? THE SLIDING-FILAMENT MODEL Each myosin has a long “tail” region and a globular “head” region The head of a myosin molecule binds to an actin filament, forming a cross-bridge and pulling the thin filament toward the center of the sarcomere Muscle contraction requires repeated cycles of this binding and release  1 Thin filament ATP Myosin head (low- energy configuration) Thick filament Figure 50.28  1 Thin filament ATP Myosin head (low- energy configuration) 2 Thick filament Myosin- Actin binding sites ADP Pi Myosin head (high-energy configuration) Figure 50.28  1 Thin filament ATP Myosin head (low- energy configuration) 2 Thick filament Myosin- Actin binding sites ADP Pi Myosin head (high-energy configuration) ADP Pi Cross-bridge 3  1 Thin filament ATP Myosin head (low- energy configuration) 2 Thick filament Myosin- The thin filament moves toward Actin binding sites the center of the sarcomere. Myosin head (low- ADP Pi Myosin head energy configuration) (high-energy configuration) 4 ADP Pi Cross-bridge 3 ADP Pi Figure 50.28  1 Thin filament ATP Myosin head (low- 5 ATP energy configuration) 2 Thick filament Myosin- The thin filament moves toward Actin binding sites the center of the sarcomere. Myosin head (low- ADP Pi Myosin head energy configuration) (high-energy configuration) 4 ADP Pi Cross-bridge 3 ADP Pi Figure 50.28  AND ….there are millions of myosin molecules in each muscle fiber (cell) many (or all) of the myosin molecules will work together to generate force - when needed the number of myosin molecules activated determines the strength of the contraction It is estimated that a single “twitch” of a muscle fiber involves 290 ATP-splitting cross-bridge cycles  the number of myosin molecules activated determines the strength of the contraction BIG question how do we regulate this? when only want to contract muscles when needed we also want to be able to control the strength of contraction What is the answer? more molecules!! troponin tropomyosin  Tropomyosin Ca2+-binding sites Actin Troponin complex What is the answer? more molecules!! troponin (a) Myosin-binding sites blocked by tropomyosin tropomyosin troponin is regulated by Ca2+ Ca2+ Myosin- binding site (b) Myosin-binding sites exposed  turning a muscle fiber on involves removing the block to actin/myosin cross linking by the tropomyosin molecule the muscle fiber achieves this by regulating the amount of Ca2+ inside the cell Ca2+ binds to the molecule troponin, which is associated with tropomyosin  remember…there are millions of actin, myosin, troponin, and tropomyosin molecules in the fiber (cell) a low concentration of Ca2+ means that only some of the troponin will have bound Ca2+. This would generate a weak contractile force a higher concentration of Ca2+ means that more of the troponin will have bound Ca2+. This would generate a stronger contractile force  OK, BUT…. where is this Ca2+ coming from? what is regulating the amount of Ca2+ in the fiber, and thereby regulating strength of contraction? We know that muscles are controlled by the nervous system. it’s time to bring muscle and nerve together they come together at the neuromuscular junction. This is a special type of synapse  where is this Ca2+ coming muscle fiber motor neurons neuromuscular junction from? what is regulating the amount of Ca2+ in the fiber, and thereby regulating strength of contraction? We know that muscles are controlled by the nervous system. it’s time to bring muscle and nerve together they come together at the neuromuscular junction. This is a special type of synapse the next slide shows a cartoon blow-up of one of these  the sarcoplasmic reticulum (SR) is a series of internal sacs within the muscle fiber this is an internal membrane enclosed compartment they function as a storage place for Ca2+ Ca2+ can be selectively released from the SR into the cytoplasm, where it will bind troponin  1 Synaptic terminal of motor neuron Plasma 1. it all starts with the arrival of Synaptic cleft T tubule membrane the action potential at the motor nerve terminus 2 Sarcoplasmic ACh reticulum (SR) all of our motor neurons release acetylcholine (ACh) Ca2+ inside SR the ACh receptor is a ligand- Ca2+ pump 3 gated channel for Na+ and K+ Ca2+ channel release of ACh will set off an action potential in the muscle 7 ATP fiber 6 CYTOSOL 2. muscle fibers are big and 4 Ca2+ have only one neuromuscular junction per fiber. The goal is to activate contraction throughout fiber. To accomplish this the action potential spreads in the fiber 5 membrane  1 Synaptic terminal of motor neuron Plasma Synaptic cleft T tubule membrane 3. Transverse tubules (T tubules) are extensions of the plasma Sarcoplasmic 2 membrane that extend into the ACh reticulum (SR) cell the action potential will Ca2+ inside SR move down the T tubules Ca2+ pump 3 Ca2+ channel 4. The T tubules are close to the SR. The arrival of the action potential in the T 7 ATP tubules is sensed by the SR, and Ca2+ channels now open 6 CYTOSOL 4 5. Ca2+ rushes out of the SR Ca2+ into the cytoplasm, where it bind to troponin….and contraction starts! 5  1 Synaptic terminal of motor neuron Plasma Synaptic cleft T tubule membrane 6. Equally important as turning contraction on, is turning it off. Sarcoplasmic 2 this is the job of the ATP ACh reticulum (SR) using Ca2+ pump. It move cytoplasmic Ca2+ back Ca2+ inside SR into the SR. Ca2+ pump 3 Ca2+ channel 7. As the Ca2+ is moved back into SR the tropomyosin now again blocks the myosin 7 ATP binding site on actin, and the muscle fiber relaxes. 6 CYTOSOL 4 Ca2+ 5 Lecture 6- MUSCULAR SYSTEM, part 2  Learning objectives for this lecture 1. Understand control of muscle contraction at both the whole muscle and single fiber 2. Understand the different types of skeletal muscle fibers and their roles 3. Understand the major differences that distinguish skeletal, smooth and cardiac muscles  1st – Let’s review Molecular Basis of Muscle Contraction 1 Thin filament ATP Myosin head (low- 5 ATP energy configuration) 2 Thick filament Myosin- The thin filament moves toward Actin binding sites the center of the sarcomere. Myosin head (low- ADP Pi Myosin head energy configuration) (high-energy configuration) 4 ADP Pi Cross-bridge 3 ADP Pi  1 Synaptic terminal of motor neuron Plasma Synaptic cleft T tubule membrane 2 Sarcoplasmic ACh reticulum (SR) and…how action potential in the Ca2+ inside SR motor neuron Ca2+ pump 3 turns on Ca2+ channel contraction 7 ATP 6 CYTOSOL 4 Ca2+ 5 CONTROL OF MUSCLE TENSION (STRENGHTH) Contraction of a whole muscle is graded; In other words the extent and strength of its contraction can be voluntarily altered There are two basic mechanisms by which the nervous system produces graded contractions: 1. Not all fibers within a muscle are activated for a contraction: It depends upon the desired strength of the contraction 2. Individual fibers can be activated to varying degrees How? By varying the amount of Ca2+ released MOTOR UNITS Spinal cord Synaptic terminals Motor Motor unit 1 unit 2 In vertebrates, each motor neuron may synapse with multiple muscle fibers, although each fiber is controlled by only one motor neuron Nerve Motor neuron A motor unit consists of a single motor axon neuron and all the muscle fibers it controls Motor neuron our muscles contain a mix of large and cell body small motor units. Which motor units get activated (recruited) depends on the task. muscles that do large strenuous tasks, Muscle Muscle fibers like those in are legs and back, have mostly large motor units (up to 1000 fibers) fine motor control, like in our fingers, requires many small motor units (10s of Tendon fibers)  MOTOR UNIT RECRUITMENT A muscle will have many motor units of varying size Recruitment is the process by which more and more motor neurons are activated in order to meet the required task (like-picking up a light load versus a heavy load) As recruitment proceeds and large motor units are activated, the force developed by a muscle increases  Regulation of tension generation in a single fiber A twitch results from a single action potential in a motor neuron. In a twitch only a few of the troponin bind Ca2+, this means only some of the actin and myosin go through cross-bridging cycles – and only a small amount of tension is generated in the muscle.  Regulation of tension generation in a single fiber The nervous system dictates that strength of contraction in each fiber. It determines this by the frequency of action potentials it sends down the motor neuron. More rapidly delivered action potentials produce increasing contraction strength through temporal summation. REGULATION OF TENSION GENERATION IN A SINGLE FIBER If action potentials are close together in time, the twitches are summed, and tension increases Twitches sum because Ca2+ pumps cannot pump the released Ca2+ back into the sarcoplasmic reticulum from before the next action potential arrives Tetanus: A state of smooth and sustained contraction produced when the rate of stimulation is so high that muscle fibers cannot relax between stimuli  1 Synaptic terminal of motor neuron Plasma Synaptic cleft T tubule membrane In other words: 2 Sarcoplasmic ACh reticulum (SR) If Ca2+ is released faster from the Ca2+ channels Ca2+ inside SR on the sarcoplasmic reticulum faster then the Ca2+ pump 3 Ca2+ channel Ca2+ pump can send it back into the sarcoplasmic reticulum, 7 ATP then the force of contraction will increase. 6 CYTOSOL 4 Ca2+ 5  POWERING MUSCLE CONTRACTION Muscles have three systems for obtaining ATP: Immediate system uses creatine- phosphate, which can rapidly generate ATP; only enough for a short burst of energy lasting a few seconds. Glycolytic system metabolizes carbohydrates to pyruvate and lactic acid Oxidative system metabolizes carbohydrates and fatty acids to H2O and CO2  Glycogen, Glycogen, glucose Creatine-P glucose or fatty acids Oxidative Creatine Kinase Glycolysis Phosphorylation (anaerobic) (anaerobic) (aerobic) aerobic = needs O2 anaerobic = does not need O2 ATP Oxygen delivery to the muscles is the limiting factor for Muscle strenuous exercise Contraction  POWERING MUSCLE CONTRACTION Glycolysis and aerobic respiration generate the ATP needed to sustain muscle contraction ­ go back and look at the actin/myosin cross-bridging cycle. Where is ATP required for force generation? ­ Where does ATP come from…..remember your first quarter of Intro Bio? ­ glycolysis: net 2 ATP generated ­ aerobic cellular respiration (oxidative phosphorylation), net 26-28 ATP  O2 this process requires the input of oxygen (it is aerobic) O2 interstitial space diffuse into muscle fiber O2 O2 interstitial space diffuse into muscle fiber O2 PROBLEM!!!! During intense exercise you can’t deliver enough oxygen to meet the needs of your muscles this why you can run at full speed for only a very short time. The muscle becomes fatigued. THE SOLUTION for short intense contractions (like On the other hand, fibers sprinting) muscles use are also capable on Creatine-P and sustained muscle anaerobic Glycolysis for ATP contraction – think of ATP generation synthesis jogging this a called the we can keep this anaerobic or glycolytic activity up as long ATP generation as we don’t exceed oxygen lactic acid not very efficient use of delivery glucose this is an aerobic muscles that use this activity pathway fatigue quickly due to the build up of lactic acid  TYPES OF SKELETAL MUSCLE FIBERS Not all muscle fibers are the same There are several distinct types of skeletal muscles, each of which is adapted to a particular function myoglobin draws in oxygen to the fiber from the interstitial fluid FAST-TWITCH AND SLOW-TWITCH FIBERS Fast-twitch fibers Slow-twitch fibers enable brief, rapid, powerful contract more slowly but sustain longer contractions contractions Fast-twitch fibers can be either glycolytic Slow fibers have less sarcoplasmic or oxidative reticulum than fast fibers and pump Ca2+ more slowly All slow-twitch fibers are oxidative  SLOW-AND FAST-TWITCH MUSCLE FIBERS Distance cyclist Sprinter Slow-twitch Fast-twitch Endurance athletes relative fiber types vary considerably from muscle to muscle and person to person. a typical person has about 45% fast twitch and 55% slow twitch fibers endurance athletes show a higher level of slow twitch fibers sprint athletes have high numbers of fast twitch fibers your fiber distribution is determined by genetically, but.. some evidence that endurance training can convert some fast twitch fibers transform into slow twitch fibers.  SKELETAL SYSTEMS TRANSFORM MUSCLE CONTRACTION INTO LOCOMOTION The skeleton provides a rigid structure to which muscles attach Skeletal muscles are attached in antagonistic pairs, the actions of which are coordinated by the nervous system The paired muscles work cooperatively Skeletons function in support, protection, and movement  CARDIAC MUSCLE Found only in the heart Consists of striated cells (they have sarcomeres) electrically connected by intercalated disks Each cell has one nucleus Cardiac muscle can generate action potentials without neural input (more on this later)  CARDIAC MUSCLE Cells are smaller than skeletal muscle cells. Cardiac muscle cells branch and interdigitate: can withstand high pressures JUNCTION BETWEEN TWO MUSCLE CELLS: INTERCALATED DISC  GAP JUNCTIONS Cardiac and smooth muscle cells are arranged in sheets. Cells in the sheet are in electrical contact via gap junctions. An action potential in one cell can spread to all others in the sheet. Synchronize contractions Figure 6.30  SMOOTH MUSCLE The simplest muscle cells structurally. Found mainly in walls of hollow organs such as those of the circulatory, digestive, and reproductive systems Contractions are relatively slow and may be initiated by the muscles themselves  SMOOTH MUSCLE Contractions may also be caused by stimulation from neurons in the autonomic nervous system Smooth muscle lacks striations because the actin and myosin are not regularly arrayed Calcium ions enter the cytosol through the plasma membrane; In other words, they do not have sarcoplasmic reticulum