Skeletal Muscle 1 PDF

KINE 2P90 Lecture 8 Skeletal Muscle 1 Friday October 4, 2024 1 Skeletal Muscle 1 - 2 Chapter 8 Skeletal Muscle: Structure and Function Structure of Skeletal Muscle (190) Neuromuscular Function (192) Muscular Contraction (194) Overv...

KINE 2P90 Lecture 8 Skeletal Muscle 1 Friday October 4, 2024 1 Skeletal Muscle 1 - 2 Chapter 8 Skeletal Muscle: Structure and Function Structure of Skeletal Muscle (190) Neuromuscular Function (192) Muscular Contraction (194) Overview Sliding Filament - Swinging Lever Arm Model (194) Energy for Contraction (194) Regulation of Excitation-Contraction Coupling (194) Excitation (196) Contraction (197) Relaxation (197) Exercise and Muscle Fatigue (200) Exercise Associated Muscle Cramps (202) Dehydration and Electrolyte Imbalance: Theory (202) Altered Neuromuscular Control Theory (202) Exercise Associated Muscle Cramps: Conclusions (203) 2 Skeletal Muscle 3 - 4 Chapter 8 Skeletal Muscle: Structure and Function Muscle Fiber Types (204) Overview of Biochemical and Contractile Characteristics of Skeletal Muscle (205) Biochemical Properties of Muscle (205) Contractile Properties of Skeletal Muscle (206) Functional Characteristics of Muscle Fiber Types (206) Slow (Type 1) Fibers (206) Fast (Type IIa and IIx) Fibers (207) Don’t Need Fiber Types and Performance (208) A Look Back Muscle Actions (209) (Huxley) Speed of Muscle Action and Relaxation (209) Clinical Force Regulation in Muscle (210) Applications 8.1 (Disease & Age) Force – Velocity/Power Velocity Relationships (212) 3 1  Figure 8.1 Structural organization of skeletal muscle 4 Figure 8.2 Microstructure of Skeletal Muscle 5 Organization of skeletal muscle Muscle ↕ Fascicles motor units ↕ Fibers ↕ Myofibrils ↕ Sarcomeres ↕ Filaments ↕ Proteins ↕ Amino Acids 6 2  Skeletal Muscle “A band of fibrous tissue in the body that has the ability to contract, producing movement in or maintaining the position of a part of the body” Miriam-Webster, 2007 “musculus” 7 Did you know? ❑ our skeletal muscles ▪ ~ 40% of total body mass ▪ ~ 20% of total metabolism ❑ the bodies “furnace” ▪ via resting thermogenesis ❑ important reservoir of Phil ▪ water Esposito ▪ amino acids ▪ carbohydrates & fats ❑ development highly regulated ▪ by myriad regulatory factors Cam Neely ❑ adaptable! ▪ training, age, disease, disuse 8 Muscle as a Motor ❑ a biological “engine” that powers ▪ breathing, pumping ▪ locomotion, posture ▪ with ~ 40% efficiency ❑ has low energy requirements at rest ▪ 10 - 15 kcal kg-1 day-1 ❑ has high energy output during exercise ▪ 1.0 - 1.5 kcal kg-1 min-1 ❑ capable of either ▪ high force, speed not at same time ▪ high endurance ❑ carbohydrate or fats is fuel ▪ waste is CO2, water and heat! 9 3 10 Muscle Fiber (Fig 8.3) sarcomere ▪ plus neuromuscular junction (next week) 11 The Muscle Fiber ❑ each is a single cell! ▪ structural/contractile proteins surrounded by membrane ❑ only 50 - 100 microns wide but can be many cm long! ▪ run tendon to tendon or aponeuroses ❑ different phenotypes possible ▪ fast vs slow fatigable vs unfatigable ❑ grouped into functional units or “families” ▪ the motor unit ❑ recruitment & activation varies ▪ helps us accomplish a wide range of tasks 12 4  The Sarcolemma ❑ phospholipid membrane encapsulates each muscle fiber ▪ barrier between cytosol and extracellular space regulates substrate entry controls ion traffic contains receptors (hormones) ❑ membrane is “excitable” ▪ generates action potential ❑ has cable properties ▪ propagates action potential ❑ contains t – tubule openings ▪ action potential “highways” ❑ disease can make more fragile ▪ muscular dystrophies 13 The Cytosol ❑ the watery medium that fills each fiber ▪ a “soup” that sets internal environment temperature, pH and ionic strength ❑ contains dissolved proteins ▪ metabolites (like ATP, ADP, Pi etc) signaling molecules o reducing equivalents ❑ permits communication ▪ between compartments ▪ between proteins ❑ fixed cytosolic water to protein ratio ▪ is this how hypertrophy works? 14 T-Tubules, Terminal Cisternae & Sarcoplasmic Reticulum ❑ transverse tubules link sarcolemma to sarcoplasmic reticulum ▪ start as openings in sarcolemma & travel transversely across fiber contain “voltage sensors” that talk to “terminal cisternae” ❑ terminal cisternae ▪ part of sarcoplasmic reticulum house calcium release channels ❑ sarcoplasmic reticulum ▪ membranous sleeve that surrounds myofibrils contains Ca2+ ❑ overall function of TTs, TC and SR ▪ structures that transduce action potential to calcium release (and eventually force) 15 5 16 The Myofibrils ❑ tubes of myofilaments arranged into sarcomeres ▪ run side by side or parallel within fiber ❑ myofilaments are contractile proteins ▪ thick and thin filaments (i.e. myosin and actin) ❑ different myofibrils segregated by ‘sleeves’ ▪ sarcoplasmic reticulum ❑ myofilaments generate muscle force ▪ at the level of the sarcomere ▪ thick and thin filaments ❑ ↑ myofbrils = hypertrophy = ↑ force ▪ but myofibril diameter is constant (myofibril number is variable!) 17 The Sarcomere ❑ the basic structural and contractile unit of the myofibril ▪ each myofibril made up of many sarcomeres stacked end to end ❑ defined as all proteins arranged between adjacent z-discs ▪ the sarcomere is essentially a 3-dimensional force generating myofilament complex ❑ z-discs are made of alpha-actinin (connective protein) ▪ chain adjacent sarcomeres together ❑ the myofilaments are parallel but interact ▪ thin filament (= actin) ▪ thick filament (= myosin) ▪ thin filaments occupy sarcomere margins ▪ thick filaments occupy sarcomere center 18 6  The Mitochondria ❑ the “power house” of the cell ▪ houses oxidative machinery bacterial origin with mitoDNA where most ATP is made ❑ mitochondrial volume varies ▪ with fiber type (slow > fast) with training (endurance > sedentary or strength) more mitochondrial volume = more endurance ❑ different fractions (dedicated) ▪ subsarcolemma why? ▪ myofibrillar ❑ communicate with cytosol ▪ ATP, ADP, Pi and Ca+ cross mitochondrial membrane 19 Muscle Fiber Volume by Compartment Structure % total Myofilaments 85 Sarcoplasmic Reticulum 5 Mitochondria 5 CHO Energy Stores 5 FFA Alterations account for different fiber function across animal kingdom 20 21 7  The Nucleous ❑ muscle fibers are multinucleate ▪ membrane bound in healthy muscle “central nucleus disease” ❑ contains muscle genome ▪ genes combine with proteins (inc. histones) to form chromosones ❑ except for mitochondrial DNA ▪ separate genome ❑ control center of the cell ▪ by regulating gene integrity ▪ by regulating gene expression 22 The Satellite Cells ❑ are muscle stem cells ▪ found above sarcolemma ❑ involved in growth and regeneration of all fiber types ▪ quiescent in undamaged muscle (no proliferation or differentiation) ▪ active in strained muscle (proliferation and differentiation) ❑ “myopotent” when active ▪ can fuse with mother fiber to donate myonuclei (= hypertrophy) ▪ can differentiate into myoblasts (= hyperplasia) 23 From Structure to Movement Filament Sliding 24 8  Sarcomere Structure to Function Contraction Requires Filament Sliding 25 26 27 9  More about Myofilaments ❑ aka the contractile proteins ▪ thick filaments mostly myosin ▪ thin filaments actin + regulatory proteins ❑ one of main sites where ATP is required ! ▪ chemical energy used to generate force via cyclic interactions of myosin with actin that cross-link myofilaments ❑ myosin ATPase regulated by stearic blocking ▪ force generated by myosin (thick filament) ▪ force regulated by actin (thin filament) ▪ titin ? 28 Sarcomere Shortening During Contraction (Fig 8.5) 29 Contractile Proteins (Fig 8.6) 30 10  Muscle Force: Generation and Regulation 31 Regulatory Proteins: Troponin C ❑ functions as a Ca2+ “sensor” ▪ binds calcium a molecular “switch” ❑ when Ca2+ occupancy is low ▪ thin filament is “off” ❑ when Ca2+ occupancy is high ▪ thin filament is “on” ❑ in Stearic Blocking Model ▪ thin filament state “off” vs “on” ▪ determines whether force is generated or not 32 Regulatory Proteins: Tropomyosin ❑ a cable like protein ▪ form “dimers” (pairs) lie in helical groove ❑ part of molecular switch ▪ position is dynamic “rocks and rolls” within groove (see animations) ❑ position influenced by TnC ▪ low Ca2+ occupancy Tm “rocks” out blocks myosin binding sites ▪ high Ca2+ occupancy Tm “rolls” in does not block myosin binding 33 11  Stearic Blocking Model: The “Gate Keeper” for Cross-bridge formation 34 Filament Sliding Animated o myofilament length stays constant o but change their relative position (↔) o the A band stays same length (↔) o the I band changes in width (↔) o question: what powers this motion? 35 Sarcomere Structure-Function Functional significance? To Sarcomere Shortening 36 12  Titin? 37 Neuromuscular Junction (Fig 8.4) Junction between motor neuron and muscle fiber ❑ Motor end plate ▪ pocket formed around motor neuron by sarcolemma ❑ Neuromuscular cleft Events leading (b) M.I. Walker/Science Source ▪ short gap between neuron and muscle fiber to action potential ❑ Acetylcholine is released from the motor neuron Fig causes an end-plate potential (EPP) and depolarization of muscle fiber ▪ 8.4 38 Take Home Points: Skeletal Muscle 1 ❑ muscles essential for life (store H20, energy, AAs and make heat) ▪ as a biological motor muscle is very efficient! ❑ each muscle fiber is a single cells with many “compartments” ▪ different compartments = different fiber types (i.e. fast and slow) ❑ myofibrils are “tubes” of contractile proteins ▪ surrounded by sarcoplasmic reticulum (Ca2+ storage/release) ▪ arranged into sarcomeres; structural & functional unit of muscle contains contractile proteins in parallel filaments (thick & thin) ❑ actin and myosin are contractile proteins ▪ stearic blocking model ▪ regulation of force between filaments ❑ sliding filament theory: structure to function ▪ cross-bridge generated; ATP powered 39 13