MD137 Muscle Lecture 1 PDF

Physiology School of Medicine 2024 Skeletal Muscle: structure & function I MD137: Principles of Lecturer: Dr K.McCullagh Physiology Learning outcomes: Describe the make-up of muscle. The Sliding Filament Mechanism. The Cross-Bridge Cycle...

Physiology School of Medicine 2024 Skeletal Muscle: structure & function I MD137: Principles of Lecturer: Dr K.McCullagh Physiology Learning outcomes: Describe the make-up of muscle. The Sliding Filament Mechanism. The Cross-Bridge Cycle. The role of ATP and calcium in cross-bridge cycling. Medical Physiology Principles for Clinical Medicine 6th Edition Main Chapters to Read for Muscle lectures Chapter 8: Skeletal Muscle and Smooth Muscle Chapter 5: Skeletal muscle Reflexes Striated Skeletal Muscle Blood vessel Muscle Fibre Vander’s Human Physiology, 14 th Ed  Overview Muscle – excitable tissues* Skeletal, Cardiac and Smooth muscle *Its membrane potential is linked to activation of that cell’s function (in this case, contraction) Adults Body Weight Skeletal muscle = 40% Heart & Smooth muscle = 10% CLASSIFICATION OF THE TYPES OF MUSCLES Somatic nervous system Autonomic nervous system (ANS)  Skeletal Muscle Functions Skeletal Muscle Function Limbs - Posture & Movement Diaphragm - Respiration Tongue - mastication, taste…. Sphincter - Constricts an opening Ocular - Eye movement Whole body - Thermogenesis* Whole body - Blood glucose Regulation *Thermogenesis: Shivering (muscle) or Non-shivering thermogenesis (brown fat).  Skeletal Muscle Defects* Muscular Dystrophies: Duchenne Muscular dystrophy Neuromuscular disorders: Myasthenia gravis Muscular atrophy: Sarcopenia / Cachexia Type II Diabetes: Insulin stimulated glucose uptake into skeletal muscle is defective *Lab Case study looking at a muscle disease and diagnosis  Structure of Skeletal Muscle Muscle fiber measures on average 100 μm in diameter and can be up to several centimeters long.  Muscle Fibers Average diameter 100 μm and up to several centimeters long Have plasma membranes called sarcolemma Are multinucleated (multiple nuclei) Are striated (stripes) – I bands: light bands – A bands: dark bands Muscle Fibers - striations Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.  Muscle Fibers Have densely packed subunits called myofibrils that run the length of the muscle fiber – Composed of thick (Myosin) and thin (Actin) myofilaments  Muscle Proteins Contractile Regulatory Structural Proteins Myosin Titin Troponin (3,700KDa, largest Actin Tropomyosin protein) Nebulin Alpha-actin Myomesin Dystrophin (427Kda, largest gene 2,200Kb)  Molecular Organization of the Sarcomere Individual muscle fibres made up of sarcomeres in series along the whole length of the muscle fibre One myosin filament is surrounded by 6 actin filaments in 3D arrangement Rhoades & Bell, 5th Edition Molecular Organization of the Sarcomere Biggest known protein Titin 3700Kda Costanzo, Physiology 6th Edition  Sliding Filament mechanism In this model when a muscle contracts, sarcomeres shorten. (Note: contraction does not always mean shortening- see next lecture) Contraction is defined as the action of the muscle to generate force – A bands do not alter in size (they reflect the myosin filament length within a sarcomere). – I bands decrease in size (they reflect actin filament that has no overlapping myosin filaments on adjacent ends of two sarcomeres) – Thin filaments slide toward the H zone. Sliding Filament mechanism  Definition 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. Sliding Myofilaments: Microscopic basis of muscle contraction Alberts et al, Molecular Biology of the cell, 2002, 4th Ed  More About Myofilaments Thick: composed of the protein myosin – Each protein has two globular heads with actin-binding sites and ATP-binding sites (ATPase activity) Myofilament components of skeletal muscle fibers  More About Myofilaments Thin: composed of the protein actin - Have proteins called tropomyosin and troponin that prevent myosin binding at rest. Myofilament components of skeletal muscle fibers (cont.)  Cross Bridges Sliding is produced by several cross bridges that form between myosin and actin. – The myosin head serves as a myosin ATPase enzyme, splitting ATP into ADP + Pi. – This allows the head to bind to actin when the muscle is stimulated due to electrical and chemical events. Cross Bridge formation S.I. Fox, Human Physiology, 13th Ed  Cross Bridge Cycle Rigor Mortis No ATP to break cross-bridge - Rigid muscle Mysosin Heads and Cross-Bridge Cycling Alberts et al, Molecular Biology of the cell, 2002, 4th Ed  Myosin heads on the myosin filament move like oars knifing through water, but do not move synchronously crossbridges myosin Actin About 50% of crossbridges make contact with actin to form the protein complex actomyosin  Regulation of Contraction Tropomyosin physically blocks cross bridges. Troponin complex: – Troponin I inhibits binding of myosin. – Troponin T binds to tropomyosin. – Troponin C binds to calcium.  Role of Calcium When muscle cells are stimulated, Ca2+ is released inside the muscle fiber. Some attaches to troponin C, causing a conformational change in troponin and tropomyosin. Myosin is allowed access to form cross bridges. Regulation of Contraction [Ca2+] C T I The calcium switch for controlling skeletal muscle contraction Muscle Relaxed ATP and Calcium Muscle both required for Contracted 10-5 M muscle contraction Intracellular Calcium Concentrations Ca2+ 10µM >100 fold increase in [Ca2+] for contraction  Summary The make-up of muscle. The Sliding Filament Mechanism. The cross-bridge cycle. The role of ATP and calcium in cross-bridge cycling.