Muscle Physiology I HSC1007 Anatomy & Physiology 1 PDF

Muscle Physiology I HSC1007 Anatomy & Physiology 1 Tan Xiang Ren, PhD Assistant Professor Health and Social Sciences [email protected] Images for illustration only. Credits to original artists. Learning Outcomes [Part I] Define the function and...

Muscle Physiology I HSC1007 Anatomy & Physiology 1 Tan Xiang Ren, PhD Assistant Professor Health and Social Sciences [email protected] Images for illustration only. Credits to original artists. Learning Outcomes [Part I] Define the function and types of muscles, and describe the structural organisation of skeletal muscles [Part II] Understand the molecular basis of skeletal muscle contraction (Sliding-Filament Theory) [Part III] Explain the role of calcium in Excitation-Contraction Coupling within muscles PART I Muscle Function & Organisation Muscle & Function Muscles are specialised tissues that can develop tension and shorten (i.e., contraction), thus producing movements. Functions: (1) Produce purposeful movements (2) Propulsion of contents through hollow internal organs (3) Emptying of contents to external environment Other Functions Maintaining posture and body position Stabilizing joints Generating heat Helps in circulation, digestion and breathing Protect internal organs Muscles Types (1) Skeletal Muscles (2) Cardiac Muscles (3) Smooth Muscles Voluntary, Striated Involuntary, Striated Involuntary, Unstriated Bundles of long, thick, Interlinked network of short, Loose network of short, cylindrical, striated, slender, cylindrical, striated, slender, spindle-shaped, contractile, multinucleate branched, contractile cells unstriated, contractile cells that extend the connected cell to cell by cells that are arranged length of the muscle intercalated discs in sheets Sherwood, 9th edition, Chapter 8 Page 252 Skeletal Muscle Organisation Image from: https://open.oregonstate.education/aandp/chapter/10-2-skeletal-muscle/ Whole Muscle Muscle Myofibril Sarcomere Muscle Fascicle Fiber (cell) Sarcomere: Functional Unit Thin &Thick Actin & Sarcomere Filaments Myosin Sarcomere Image from: https://open.oregonstate.education/aandp/chapter/10-2-skeletal-muscle/ Sarcomere Bands Orientation of filaments Actin Cross bridge Myosin Sherwood, 9th edition, Chapter 8  Actin (Thin filament) Myosin cross bridge binding site Blocked Actin Troponin Exposed When Ca2+ binds to troponin, the shape of this protein is Tropomyosin changed in such a way that tropomyosin slips away from its blocking position, thus exposing the binding site for myosin. Sherwood, 9th edition, Chapter 8 Myosin (Thick Filament) One myosin protein consists of two identical intertwined, golf club like subunits. The heads of myosin form the cross bridge. Sherwood, 9th edition, Chapter 8 Role of ATP as energy currency ADP Muscle fibers have alternate pathways for forming ATP ATP production (1) Transfer of a high-energy phosphate from creatine phosphate to ADP Regenerates ATP during Exercise (2) Glycolysis (3) Oxidative phosphorylation Aerobic vs Anaerobic During high intensity exercise Lactic Acid (2) Glycolysis Fermentation [No need O2] Cytosol Supports Prolonged exercise Krebs 32 Cycle ATP Mitochondrion (3) Oxidative phosphorylation [Requires O2]  RECAP for Part I ✓Muscles are specialised tissues that can contract. They produce movements and/or move contents within or out of our body. ✓Whole muscle > Muscle Fascicle > Muscle Fibers > Myofibrils > Sarcomere > Thick and thin filaments > Actin and Myosin ✓ATP is the energy currency for muscle contractions, and it can be produced with or without oxygen by the muscles. PART II Molecular basis of skeletal muscle contraction Sliding Filament Theory Sliding of thick and thin filaments to be overlapped with each other Sarcomere as single contractile unit Multiple sarcomere units shortening will generate the contraction of a muscle. Changes in size of sarcomere bands Sherwood, 9th edition, Chapter 8 Presence of Ca2+ regulates actin-myosin binding [Formation of cross bridges] Allows the myosin thick filament to pull on the thin filament Sherwood, 9th edition, Chapter 8 Power stroke Stroking motion of myosin head pulls the thin filament toward the center of the sarcomere Repeated cross-bridge binding and power stroke shorten the muscle. Sherwood, 9th edition, Chapter 8 Role of ATP (1) Detachment from actin (2) “Cocking” of the myosin head – to be ready for power stroke (i.e., storing potential energy) Putting it all together… Cyclic transition between power stroke and detachment [Cross-bridge cycling] Sherwood, 9th edition, Chapter 8 What happens when there is no ATP? Rigor mortis (stiffness of death). Muscles remain contracted. Asynchronous cross-bridge cycling Cross bridges do not all stroke in unison. At any time during contraction, part of the cross bridges are stroking, while others are returning to their original conformation to prepare for binding with another actin. What about other muscles? Smooth muscles [involuntary, unstriated] Single-unit smooth muscle is myogenic - pacemaker and slow- wave potentials Smooth muscle contraction differs from that of skeletal muscle: Modification of smooth muscle activity by the autonomic nervous system Arrangement of thick and thin filaments Ca2+ dependent phosphorylation of myosin No troponin on actin filament in smooth muscle, Presence of intermediate filaments Sherwood, 9th edition, Chapter 8 Ca2+-dependent phosphorylation of myosin light chain Activation of enzyme to add phosphate to the myosin light chain Sherwood, 9th edition, Chapter 8 Characteristics of Smooth Muscle Smooth muscle can still develop tension, yet inherently relaxes when stretched Stress relaxation response - rearrangement of cross- bridge attachments to restore tension Smooth muscle is slow and economical Latch phenomenon: stay attached longer, saves ATP What about other muscles? Cardiac muscles [involuntary, striated] Found only in the heart Cardiac muscle blends features of both skeletal and smooth muscle – also myogenic Heart is innervated by the autonomic nervous system Highly organized, striated, slender, and short fibers Interconnected by gap junctions found in intercalated discs that join cells together Functional syncytium: Beating as one From: https://www.lecturio.com/concepts/cardiac-physiology/  RECAP for Part II ✓Sliding filament theory: Myosin thick filament pulling on actin thin filaments to shorten the sarcomere ✓Asynchronous cyclical transition between power stroke and detachment requires ATP molecules ✓Smooth muscles and cardiac muscles are involuntary and myogenic, and they show differences from skeletal muscle contraction. PART III Excitation- contraction coupling: Role of Ca 2+ Excitation of skeletal muscles Brain Central motor drive “Move!” Action potential propagating along membrane Motor Neuron Motor End Plate (neuromuscular junctions; NMJ) Acetylcholine (ACh) Muscle T-tubules & SR Action potential propagating along membrane Sacs that contain Ca2+ Receptors Arrival of action potential T tubules contain Dihydropyridine Receptors (DHPR; voltage-gated calcium channel) SR contains Ryanodine Receptors (RyR; calcium releasing channels) Calcium-induced Calcium release Calcium ions released from SR into the cytosol (now in contact with the myofibrils – induce contraction!) Excitation- contraction coupling Calcium-induced Calcium release (1) (2) (3) Bers, D. Nature 415, 198–205 (2002) If Ca2+ is always present, what happens? Induce contractions persistently Reuptake Active reuptake of Ca2+ via SERCAs Sarco/Endoplasmic Reticulum Release Ca2+-ATPase. Muscle relaxation Contraction outlasts the electrical activity (AP) that initiated it. 30-100 msec (1) Time before onset of contraction (Ca2+ release) (2) Time for generating tension by cross-bridge activity 1-2 msec (3) Time for reuptake of Ca2+ Role of Ca2+ in muscle contraction 1) Calcium-induced calcium release from SR lateral sacs (effects on DHPR and RyR) – EC coupling 2) Calcium binding to troponin for conformational change to expose cross-bridge binding sites 3) [Smooth muscle] – Calcium-dependent phosphorylation of myosin light chain  RECAP for Part III ✓Excitation of muscles involves arrival of action potential at T-tubules and the induction of calcium release from SR. ✓Calcium is the link between excitation and contraction (EC coupling) ✓Muscle relaxation requires the removal/reuptake of calcium back into SR. What have I learnt so far? 1. How are skeletal muscles organised? 2. How do skeletal muscles contract? 3. How are calcium & ATP important for muscle contraction? 4. How are smooth and cardiac muscles different? Muscle Physiology II HSC1007 Anatomy & Physiology 1 Tan Xiang Ren, PhD Assistant Professor Health and Social Sciences [email protected] Images for illustration only. Credits to original artists. Covered in Lecture 1 ✓Muscle organisation and function ✓Sliding filament theory ✓Excitation-contraction coupling ✓Role of calcium and ATP in muscle contractions Learning Outcomes (2) [Part I] Properties: Describe the different muscle fiber types and characteristics [Part II] Mechanics: Describe the types of muscular contractions Understand load-velocity and length-tension relationships [Part III] Motor control: Describe the afferent information received from muscles Explain the mechanisms of reflexes PART I Muscle Properties: Fiber types Muscle Fiber Types 1. Slow-oxidative (Type I) fibers Slow Twitch Fibers 2. Fast-oxidative (Type IIa) fibers Fast Twitch Fibers 3. Fast-glycolytic (Type IIx) fibers Fiber characteristics are primarily dependent on ATP hydrolysis and synthesis. Comparing Muscle Fibers Fast Versus Slow Fibers The higher the Myosin-ATPase activity, the more rapidly ATP is split and the faster the rate at which energy is made available for crossbridge cycling. Oxidative Versus Glycolytic Fibers Oxidative muscle fibers are more resistant to fatigue than glycolytic fibers. Genetic endowment: Most contain a mixture of all three fiber types - the % of each type is largely determined by the type of activity for which the muscle is specialized. Some of us are built to be “Sprinters” or “Marathoners”. Chicken vs Cow? [White vs Red meat] Muscle Adaptations (1) Muscle fibers adapt considerably in response to demands placed on them Improvement in oxidative capacity (aerobic endurance exercise) Blood supply Muscle hypertrophy (anaerobic high intensity resistance training) Increased Influence of testosterone Cross- (Promotes synthesis and assembly sectional of myosin and actin) area Jorgenson et al., Cells. 2020 Jul 9;9(7):1658. Muscle Adaptations (2) Interconversion Between Fiber Types Type IIa fibers ↔ Type IIx fibers Slow and fast fibers are generally not interconvertible (except under special circumstances e.g., spinal cord injury or lower gravity in space) Repair of muscle (satellite cells become myogenic precursor cells under muscle damage) Muscle atrophy (disuse, denervation, aging) Use it or lose it!  Sarcopenia Gradual muscle loss after the 4th decade of life Loss through inactivity comprises 1% per year, accelerating even more so, in males, after age 50 Loss in both size and number of muscle fibers https://www.singhealth.com.sg/news/defining- med/combating-sarcopenia Loss of muscle mass is permanent and can affect activities of daily living and bone mass later in life  RECAP for Part I ✓Characteristics of muscle fibers (Type I, Type IIa, Type IIx) ✓Muscles adaptation to exercise training (improved oxidative capacity, hypertrophy and fiber conversion) ✓Muscles can be repaired after damage or can be lost (atrophied) due to disuse, disease or aging. PART II Muscle Mechanics: Contractions Contraction of Whole Muscles Whole muscles = groups of muscle fibers tendon bundled together and attached to bones passive Tough, collagenous tendons attach muscles elasticity to bones Tension is produced internally within sarcomeres Muscle tension transmitted to bone as it tightens the series-elastic component (tendon) By John Moore From- https://en.wikipedia.org/wiki/File:Irish_600kg_euro_chap_2009.JPG, CC BY-SA 3.0, Lever system Interactive units of skeletal muscles, bones, and joints form lever systems: Origin Bones are levers Joints are fulcrums Insertion Skeletal muscles provide the force to move the bones https://www.visiblebody.com/blog/biomechanics-lever-systems-in-the-body Amplification of velocity Disadvantage: and distance (x7)! larger force needed Sherwood, 9th edition, Chapter 8 Primary Types of Contraction Isotonic (i.e., constant tension): load remains constant as the muscle length changes Isometric (i.e., constant length): muscle length remains constant as tension increases Isokinetic (i.e., constant motion): velocity remains constant as the muscle fibers shorten From: https://www.osmosis.org/learn/Biomechanics:_Muscle_contractions Other Types of Contraction Concentric contraction - Muscle shortens under load Eccentric contraction - Muscle lengthens under load Some skeletal muscles do not attach to bones at both ends but still produce movement (e.g., tongue muscles) Exercise-induced muscle damage Eccentric exercises are more likely to damage muscles Ultrastructural damage – e.g., sarcomere disruption, loss of Z lines, Z line streaming, widening of distance between thick and thin filaments. Fast twitch/Type II fibers are more susceptible to eccentric exercise induced damage due to smaller sarcomeric proteins. Choi SJ. Differential susceptibility on myosin heavy chain isoform following eccentric-induced muscle damage. J Exerc Rehabil. 2014 Dec 31;10(6):344-8. Extensive area of sarcomere disruption Newham et al. 1983 Sep;61(1):109-22. doi: 10.1016/0022-510x(83)90058-8. Load-velocity relationship Load–velocity relationship in concentric contractions. Much energy used Inverse by muscles is relationship converted to heat. for eccentric 25% external work contraction 75% heat The heavier the load, the slower you can lift it. Graded Contractions Contractions of a whole muscle can be of varying strength based upon: (1) Number of muscle fibers contracting (2) Amount of tension developed by each contracting fiber Motor Unit Recruitment 1 motor unit = one motor neuron plus all the muscle fibers it innervates More motor units recruited, stronger contraction (increasing No of muscle fibers contracting) Smallest to Largest Motor Units Least Fatigable to Most Fatigable Factors influencing amount of Muscle Tension 1. Frequency of stimulation 2. Length of the fiber at the onset of contraction 3. Extent of fatigue 4. Thickness of the fiber (1) Frequency of simulation→ Twitch summation How? (1) Sustained elevation in cytosolic Ca2+ (2) More time to stretch series- elastic component (transmit tension) (2) Optimal Muscle Length for Maximal Tension Optimal Muscle length (lo) → maximal no. of myosin cross bridges and actin accessible for binding and pulling Too short – overlap of “Just nice” filaments, non-ideal mechanics Too long – “unused/unmatched” cross-bridges and actin. (3) Extent of Fatigue Inability to maintain muscle tension at a given level Fatigue may be of peripheral (muscle) or central origin Exercising muscle can no longer respond to stimulation with the same degree of contractile activity (local increase of phosphate, leakage of Ca2+, depletion of glycogen) Central fatigue occurs when the CNS no longer adequately activates motor neurons (4) Thickness of Fiber Size of myofibers e.g., Strength/Resistance training Number of myofibers e.g., Testosterone, Steroids, vigorous weight training Jorgenson et al., Cells. 2020 Jul 9;9(7):1658.  RECAP for Part II ✓Muscles rely on a lever system (joint, muscle, load). ✓Isometric / Isotonic / Isokinetic and Concentric / Eccentric contractions ✓Number of muscle fibers contracting, and Amount of tension developed by each fiber determine the force of contraction. PART III Motor Control: Muscle Spindles, Golgi tendon organs and Reflexes Control of motor activity Movements (1) Voluntary Brain (2) Reflexes Automatic (3) Rhythmic Spinal Cord Central pattern generators to drive rhythmic patterned Motor Neurons outputs e.g., Walking Skeletal Muscles Central Nervous system Afferent Inputs For effective control of motor output, the CNS needs continual information regarding ongoing changes in muscles. Understanding relative position and movement of the body (Proprioception) - balance 1. Muscle length (Muscle spindles) 2. Muscle Tension (Golgi Tendon Organs) Muscle Spindles Extrafusal fibers (“ordinary” muscle fibers) Intrafusal fibers (muscle spindles)  Afferent neuron (for sensing length changes) Gamma Motor Neuron (to contract intrafusal fibers) Alpha Motor Neuron (to contract extrafusal fibers) Alpha gamma coactivation to maintain tension in muscle spindle Relaxed Muscle Contracted Muscle Contracted Muscle “hypothetical” “actual” Gamma Alpha Alpha A “Slack” Muscle spindle cannot Maintaining a “Taut” communicate change in length muscle spindle Golgi Tendon Organ Tension gauge (the point where tension is transmitted to bone to move it) Stretch Reflex Patellar tendon reflex To sense and resist changes in muscle length - stabilize our balance, maintain posture Withdrawal Reflex Mediated at Spinal Cord Level Agonistic Antagonistic Crossed Extensor Reflex “Opposite” muscular contractions to bear weight on uninjured limb  RECAP for Part III ✓Skeletal muscles are controlled by CNS motor signals. ✓Muscle spindles convey muscle length while Golgi Tendon Organs convey muscle tension ✓Reflexes are mediated at the spinal cord level and can help us to retain balance and avoid danger. What have I learnt so far? 1. What are the different muscle fibers and properties? 2. How do they create body movements? 3. Why and how does the muscle strength varies? 4. How are skeletal muscles controlled and what information are important for them to function properly?