MNB.6 Muscle Ultrastructure and Biochemistry of Movement PDF
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RCSI University of Medicine and Health Sciences
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Dr. Tom Hodgkinson
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This document provides a detailed explanation of the muscle ultrastructure and biochemistry of movement by an RCSI University of Medicine lecturer. It covers various topics regarding muscle mechanics.
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Musculoskeletal System, Nervous System & Bioelectricity MNB.6 Muscle ultrastructure and biochemistry of movement N A M E : D r. To m H o d g k i n s o n Learning outcomes At the end of this lecture, the learner will be able to Discuss the detailed ultrastructure of skeletal muscle, myofibrils...
Musculoskeletal System, Nervous System & Bioelectricity MNB.6 Muscle ultrastructure and biochemistry of movement N A M E : D r. To m H o d g k i n s o n Learning outcomes At the end of this lecture, the learner will be able to Discuss the detailed ultrastructure of skeletal muscle, myofibrils and myofilaments Describe myosin and actin molecular structure Describe the sliding filament theory of Huxley and Huxley Outline the biochemistry of the ratchet mechanism of muscle action MNB.6 Muscle ultrastructure and biochemistry of movement 2 Muscle Ultrastructure Muscle ultrastructure: a complex arrangement of many protein-protein interactions. The sarcomere is the basic repeating unit of muscle MNB.6 Muscle ultrastructure and biochemistry of movement 3 Muscle Ultrastructure Each fibre is enclosed in a special cell membrane called the sarcolemma Each muscle fibre contains smaller myofibrils embedded in the cytoplasm of the fibre The cytoplasm (cytoplasm) is called the sarcoplasm MNB.6 Muscle ultrastructure and biochemistry of movement 4 Main Components Muscle Fiber Cytosol = Sarcoplasm - In muscle known as sarcoplasm - Rich in glycogen, ATP, Creatine Phosphate, glycolytic enzymes Transverse tubules (T-tubules) - Series of membranous folds extending from plasma membrane - Transmit electrical signal Sarcoplasmic Reticulum (SR) - Flattened vesicles which surround each myofibril - Sequester (collect) calcium MNB.6 Muscle ultrastructure and biochemistry of movement 5 Muscle Ultrastructure MNB.6 Muscle ultrastructure and biochemistry of movement 6 Muscle Ultrastructure Myofibrils are 1 µm in diameter and divided by conspicuous light and dark bands The light band is called the I-band (isotropic); the dark band the A-band (anisotropic) In the middle of the I-band is a dark line the Z-line/Z disc The unit of contraction, the sarcomere, extends between Z-lines. MNB.6 Muscle ultrastructure and biochemistry of movement 7 Muscle Sarcomere The basic contractile unit of muscle fiber. Each sarcomere is composed of two main protein filaments—actin and myosin—which are the active structures responsible for muscular contraction. Gives skeletal muscle the striated appearance under the light microscope Made up of parallel and overlapping proteins, the location of which gives the dense or light appearance to the myofibril 2 main filamentous components: - Actin (thin filaments) - Myosin (thick filaments) MNB.6 Muscle ultrastructure and biochemistry of movement 8 Muscle Sarcomere Ultrastructure Sarcomere H Band M Line Z Line Thin Filaments Thick Filaments A Band I Band MNB.6 Muscle ultrastructure and biochemistry of movement 9 Molecular Structure of Thin Filament (Actin) The thin filament is made up of three different components: A double stranded F-actin (filamentous-actin) protein molecule wound into a double helix A double stranded -helical protein molecule tropomyosin, lying in the groove of the F-actin helix A third, troponin, consisting of 3 globular proteins (TnC, TnI, TnT) periodically attached to the tropomyosin strand MNB.6 Muscle ultrastructure and biochemistry of movement 10 Actin and Myosin interaction – Sliding Filament Theory MNB.6 Muscle ultrastructure and biochemistry of movement 11 Thin Filament Arrangement Tropomyosin and troponin regulate actin In the resting state the tropomyosin strands cover the myosin binding sites on actin One of the troponin proteins (TnT) binds to the tropomyosin; one (TnI) binds to F-actin; the third (TnC) binds to Calcium (Ca2+) ions MNB.6 Muscle ultrastructure and biochemistry of movement 12 Thin Filament Arrangement When Ca2+ is released from the sarcoplasmic reticulum, it binds to TnC This initiates the moving of tropomyosin from the myosin binding site Myosin is now able to bind to actin MNB.6 Muscle ultrastructure and biochemistry of movement 13 Myosin Filaments (Thick Filaments) About 400 myosin polypeptides; approx 200 each side of the M-line Consists of: - A compact ‘head' region - A long ‘tail' region composed of two -helices The tails pack together to form the thick central portion of the myosin filament The heads stick out to form 'cross bridges' with the actin filaments Most of the tail is called light meromyosin The head and some of the tail is composed of heavy meromyosin Myosin forms the A-band https://www.youtube.com/watch?v=7Nh 2FfqDZT4 MNB.6 Muscle ultrastructure and biochemistry of movement 14 Molecular Structure Of Myosin Myosin molecules comprise two heavy chains and four light chains. The C-terminal parts of the myosin heavy chains (MHC) twist together to form the 1500 Å-long coiled-coil α- helical rod-shaped tail domain. The N-terminal parts of the heavy chains form the two myosin heads. Each head behaves as an enzyme binding to ATP and subsequently hydrolysing it The myosin head stores energy in the form of ADP and inorganic phosphate-Pi MNB.6 Muscle ultrastructure and biochemistry of movement 15 Sliding Filament Theory In 1950, A. F. Huxley and H. E. Huxley independently proposed a theory to explain how muscle fibers contract - it is called the sliding filament theory. Sliding Filament Theory Myosin filaments use energy from ATP to “walk” along the actin filaments with their cross bridges. Contraction is due to the actin and myosin filaments sliding between each other The force of contraction is caused by the movement of the cross-bridges This pulls the actin filaments closer together MNB.6 Muscle ultrastructure and biochemistry of movement 16 Sliding Filament Theory 1. When a nerve signal reaches the muscle cell, calcium is released from the sarcoplasmic reticulum surrounding the myofibrils. 2. Calcium causes a conformational change in the tropomyosin molecule which shift in position to expose the binding sites (dark green) of the actin proteins. 3. The myosin heads bind to the binding sites of the actin proteins, to form a cross-bridge as the inorganic phosphate is released. 4. ADP is released which causes initiation of the power stroke, where the thin filament gets pulled closer toward the midline of a sarcomere. 5. A new ATP molecule binds to the myosin head causing the separation of the actin-myosin cross-bridge. The ATP is subsequently hydrolyzed to ADP and inorganic Phosphate (step 1) and the energy transferred from the ATP to the myosin head causes it to pull back like the trigger of a gun. 6. This contraction cycle will continue until the nerve signal stops, and calcium is reabsorbed back into the sarcoplasmic reticulum, which causes the tropomyosin molecules to cover the actin binding sites, stopping the myosin to form new cross-bridges. MNB.6 Muscle ultrastructure and biochemistry of movement 17 Sliding Filament Theory (a) Resting pattern of myofilaments (b) As contraction commences increased overlap between actin and myosin filaments (c) As the sarcomeres shorten the muscle fibres shorten MNB.6 Muscle ultrastructure and biochemistry of movement 18 Muscle Sarcomere Ultrastructure I band A I band band Result: During muscle contraction The A-band remains the same length The I-band shortens The H-zone is reduced or disappears MNB.6 Muscle ultrastructure and biochemistry of movement 19 Ratchet Mechanism of Contraction Describes the biochemical and biophysical events which occur during contraction Conversion of the energy of ATP molecules into the physical work of the displacement of the actin and myosin relative to each other Formation of cross-bridges between the myosin head and the myosin binding site on the actin filament MNB.6 Muscle ultrastructure and biochemistry of movement 20 Ratchet Mechanism Powerstroke Cross-bridge action: Attachment of myosin ‘Contraction’ of myosin head Breaking of actin/myosin interaction Re-attachment further along the actin filament at the next active site Contraction of myosin head Conformational change occurs in the myosin head which translates chemical energy into physical work ATP ADP + inorganic phosphate + Energy The powerstroke drags the actin filament along some 5 - 12nm towards the M-line MNB.6 Muscle ultrastructure and biochemistry of movement 21 Ratchet Mechanism One ATP molecule is used per myosin head for each powerstroke achieved However, the release of the ADP + Pi is slow without actin The events in the myosin head can be depicted in a cyclical fashion In resting muscle most of the myosin is in the Myosin-ADP - Pi form and the myosin binding site on actin is inhibited by troponin and tropomyosin 1. Actin is uncovered through the binding of Ca2+ to troponin. The Myosin-ADP - Pi complex binds to actin 2. This releases Pi, producing the powerstroke at the cross-bridge. The myosin head changes conformation 3. Immediately another ATP molecule replaces ADP in the myosin head, binding to the actomyosin complex to form an A-M-ATP complex (not shown) 4. The actin is released. The myosin head reverts to the resting conformation 5. ATP is hydrolysed to ADP – Pi; the resting state MNB.6 Muscle ultrastructure and biochemistry of movement 22 Excitation-Contraction Coupling (ECC) Describes the rapid communication between electrical events occurring in the plasma membrane of skeletal muscle fibres and Ca2+ release from the sarcoplasmic reticulum, which leads to contraction This depolarizes the sarcolemma and the wave of depolarization passes inward via the T-tubule system The sarcoplasmic reticulum next to the T-tubules is now affected and Ca2+ ions are released from the terminal cisternae through ion channels into the sarcoplasm MNB.6 Muscle ultrastructure and biochemistry of movement 23 Excitation-Contraction Coupling (ECC) The initial signal for muscle contraction is the release of the chemical acetylcholine (ACh) at the neuromuscular junction (NMJ) MNB.6 Muscle ultrastructure and biochemistry of movement 24 Excitation-Contraction Coupling (ECC) Ca2+ binds to Troponin-C (TnC) which in turn affects Troponin-I (TnI), bound to F-actin. The TnI disengages from actin thereby causing a conformational change in tropomyosin, uncovering the active sites on F-actin This results in muscle contraction and ATP hydrolysis Ca2+ is pumped back into the sarcoplasmic reticulum, removing it from the myofiber The Muscle relaxes MNB.6 Muscle ultrastructure and biochemistry of movement 25 Anaesthetics Muscle Relaxants Two types of muscle relaxants used in anaesthesia: 1. Depolarizing muscle relaxants - Cause contraction of the muscle once, but prevent further contractions - E.g. Suxamethonium 2. Non-depolarizing muscle relaxants - Prevent muscle from contracting - E.g. Tubocurarine MNB.6 Muscle ultrastructure and biochemistry of movement 26 Learning outcomes Discuss the detailed ultrastructure of skeletal muscle, myofibrils and myofilaments Describe myosin and actin molecular structure Describe the sliding filament theory of Huxley and Huxley Outline the biochemistry of the ratchet mechanism of muscle action MNB.6 Muscle ultrastructure and biochemistry of movement 27 Thank you F O R M O R E I N F O R M AT I O N P L E A S E C O N TA N T N A M E : D r. To m H o d g k i n s o n EMAIL: [email protected] 28