Module 4 - Muscle Physiology PDF

FACULTY OF HEALTH KINESIOLOGY AND HEALTH SCIENCE MODULE 4 – MUSCLE PHYSIOLOGY HH/KINE 2011 - HUMAN PHYSIOLOGY I Fall 2024 MODULE 4 – MUSCLE PHYSIOLOGY...

FACULTY OF HEALTH KINESIOLOGY AND HEALTH SCIENCE MODULE 4 – MUSCLE PHYSIOLOGY HH/KINE 2011 - HUMAN PHYSIOLOGY I Fall 2024 MODULE 4 – MUSCLE PHYSIOLOGY Dr. Paris 104 MODULE 4 – MUSCLE PHYSIOLOGY Human Physiology, Nelson 4th Edition Chapter 7, Pages 297-322 5th edition, Chapter 8 105  End of Module 3 MODULE 4 – MUSCLE PHYSIOLOGY Module 4: How does an action potential cause muscle contraction? 106 Learning Objectives By the end of this section, you should be able to: – Describe the macro- and micro-architecture of skeletal muscle – Understand the molecular basis of skeletal muscle contraction  Muscle can develop tension and shorten = Muscle contraction Largest group of tissues in our body: About 50% of our body mass (Skeletal muscle ~35 to 40%) MODULE 4 – MUSCLE PHYSIOLOGY 107  Skeletal muscle - striated A myofibre is formed by the fusion of undifferentiated and mononucleated cells = Myoblasts MODULE 4 – MUSCLE PHYSIOLOGY => A single muscle cell = A muscle fibre or myofibre. => One single cylindrical, relatively large and elongated, multinucleated cell. In adults = 20-100µm diameter, up to 20 cm length (varies greatly) Microscope => Alternating light bands perpendicular to the long axis. Cardiac and skeletal muscle = striated muscles. Cardiac muscle - Binds cells together - Allows cells to communicate 108 with each other  Composition of muscle = all of the muscle fibres bound together by layers of connective tissue. Muscle Tendon (collagen fibres) MODULE 4 – MUSCLE PHYSIOLOGY Tiers: Muscle Muscle fibre Fascicle (a single (group of cells) muscle cell) Muscle fibre (a single cell) Fascicle Myofibril Connective (inside cells) tissue Layers of connective tissue epimysium binds entire muscle; perimysium binds groups of 110 fibres/cells or ‘fascicles‘; endomysium binds individual cells  What gives muscle its ‘striations’? Arrangement of numerous thin and thick filaments, composed of the contractile proteins actin (thin filaments) and myosin (thick filaments), respectively. They are located in the cytoplasm in long links MODULE 4 – MUSCLE PHYSIOLOGY called ‘myofibrils' (80% of the volume of the muscle). Filaments are arranged in a repeating pattern along the length of the myofibril. One unit of this repeating pattern = Sarcomere (functional unit of the muscle). Dark A band Muscle fibre Light I band Myofibril Sarcomere Relationship of a muscle fibre and a 111 myofibril  A and I Bands Thick filaments are located in the center of the sarcomere => Wide dark MODULE 4 – MUSCLE PHYSIOLOGY band = A band. For each sarcomere => Two sets of thin filaments, one at each end, that are anchored to a network of connecting proteins = Z line. The other extremities overlap a portion of the thick filaments. One sarcomere: Between two Z lines. Lighter band = I band = Between the ends of the bands A where thin filaments do not overlap the thick ones. H Zone: Center of the band A where without any thin filament overlaping the thick ones. The sarcomere is the functional unit of skeletal muscle (i.e the smallest component that can contract in the myofibre) 112  MODULE 4 – MUSCLE PHYSIOLOGY 113  The thick filaments of myosin are anchored in place by titin fibres; and thin filaments called actin are anchored to Z-lines (Z-lines have MANY types of MODULE 4 – MUSCLE PHYSIOLOGY anchoring proteins). Titin: the largest protein in the body! ~27,000 amino acids Molecular weight of 3 million daltons 114  Tropomyosin and troponin are important regulatory molecules for contraction = Bind to the thin actin filaments. MODULE 4 – MUSCLE PHYSIOLOGY 115  Notion of cross-bridge = Portion of myosin molecule (thick bands) that extend to reach the thin actin filaments. MODULE 4 – MUSCLE PHYSIOLOGY = This will enable the muscle contraction. The sliding movement => Thin filaments move toward the center of the sarcomere. => Myosin’s cross-bridges bind to actin; the crossbridges then flex to slide actin. 116  A cross section through a sarcomere shows that: each myosin can interact with 6 actin filaments, and each actin can interact with 3 myosin filaments. MODULE 4 – MUSCLE PHYSIOLOGY 117 Longitudinal view Cross-sectional view  How does a muscle contract? Muscle contraction does not necessarily cause “shortening” of the muscle Contraction = Activation of force-generating actin-myosin cross-bridge cycling within muscle fibres. MODULE 4 – MUSCLE PHYSIOLOGY After contraction = Relaxation Mechanism? => Sliding-filament mechanism (caused by cross-bridge cycling) When force generation produces shortening of skeletal muscle fibres => Overlapping thick (myosin) and thin (actin) filaments in each sarcomere moves past each other => movement of the cross-bridge. => Sliding-filament mechanism. The sliding filament mechanism is the result of the action potential stimulating skeletal, smooth, and cardiac muscles. Changes in the membrane potential of muscles are linked to internal changes in calcium release (and contraction). In all three types of muscle, myosin and actin interactions are regulated by the availability of calcium ions. 118  Structure of the actin molecule: globular molecule = one single polypeptide (‘long chain of amino acids’). They polymerize to generate a long actin filament => two intertwined helical chains. Each actin molecule contains a binding site for the thick filament myosin. MODULE 4 – MUSCLE PHYSIOLOGY 1 actin molecule = 1 globule 1 actin helix = many globules linked together Regulatory molecules: Troponin and Tropomyosin 119  What is troponin? MODULE 4 – MUSCLE PHYSIOLOGY About 7 actin molecules In relaxed skeletal muscle, tropomyosin blocks the cross-bridge binding site on actin. Partially covers the myosin-binding sites on each actin molecules Each tropomyosin molecule is hold in such inhibitory binding position by the troponin molecule The troponin has three subunits: T, I, C. 1. T, tropomyosin = Interaction with the tropomyosin molecule 2. I, Inhibitory = Inhibitory grip that prevents tropomyosin from moving along actin. 3. C, Calcium = Binding site for calcium. Both tropomyosin and troponin cooperatively block any interaction between myosin cross-bridge and actin filament in a resting myofibre. 120  Structure of the myosin molecule: Two large polypeptide heavy chains + four smaller light chains. They combine to generate a large molecule with two globular heads and one long tail. These globular heads are the site where a cross-bridge with actin forms MODULE 4 – MUSCLE PHYSIOLOGY Each globular head Heavy chain: - 1 tail, 1 head Two binding sites 1. One for actin Light chain: 2. One for ATP - Specialized proteins that stabilize the head (also a 100 nm site of regulation) Note: In muscle physiology, sometimes ‘cross bridge’ refers to the myosin head (the site of cross bridge formation), other times it refers to the binding between myosin to actin. (Example: a ‘hook’. It can be the actual object or the action) 121  The ATP binding site also has an enzymatic activity: ATPase Energy for contraction MODULE 4 – MUSCLE PHYSIOLOGY The myosin molecules in the two ends of each thick filament are oriented in opposite directions => The power strokes of the cross-bridges move the thin filaments toward the centre of the sarcomere. Molecular basis of skeletal muscle contraction Sequence of events: = Cross-bridge cycle 1) binding between the myosin head and the thin filament, 2) movement of the cross-bridge (Power stroke), 3) detachment of the cross-bridge: detach myosin from the thin filament, 4) Re-energize the myosin head so it can re-attach to a thin filament to repeat the cycle. 122 MODULE 4 – MUSCLE PHYSIOLOGY Note: here, the text refers to the myosin head as ‘cross bridge’ Sliding filament mechanism of muscle contraction 123  MODULE 4 – MUSCLE PHYSIOLOGY 124 (myosin heads)  MODULE 4 – MUSCLE PHYSIOLOGY 125  End of Module 3 MODULE 4 – MUSCLE PHYSIOLOGY Module 4: How does an action potential cause muscle contraction? 132