Exercise Physiology KINS 4940 Muscle Physiology PDF

Exercise Physiology KINS 4940 Dongwoo Hahn, PhD 9 Muscle physiology Goals of this chapter Understand the structure-function relationship of muscle Understand the three different muscle types Understand the process of muscle contraction mechanism Understand the twitch...

Exercise Physiology KINS 4940 Dongwoo Hahn, PhD 9 Muscle physiology Goals of this chapter Understand the structure-function relationship of muscle Understand the three different muscle types Understand the process of muscle contraction mechanism Understand the twitch types of muscle fibers Apply the knowledge to exercise and pathology model of muscle Order of lecture & your study Structure Function Measurement 1. Structure of muscle Anatomy of muscle Interstitial connective tissue Epimysium → Perimysium → Endomysium Composition: mostly collagen fibers Intermolecular cross-linking: stiffness Structure in sarcolemma Basement membrane Collagen IV Laminin Muscle fiber Dystrophin glycoprotein complex Dystroglycans Sarcoglycans Dystrophin Critical connection between ECM, sarcolemma, and cytoskeleton  Intermediate filaments Desmin Connection among myofibers Sarcomere alignment with contraction Linking cytoskeletal network Connect organelles Nuclei, mitochondria - myofibers Myotendinous junction Longitudinal fiber – tendon force transmission Finger-like projections Surface area ↑ Molecular organization similar to the lateral connection of sarcomere-sarcolemma-ECM- endomysium  Force transmission: longitudinal & lateral Key protein for lateral force transmission ( ) Sarcomere, myofibril, ECM, inactive fibers Key protein for longitudinal force transmission ( ) Thick/thin filaments, Z-line, myotendinous junction 80-95% of Inactive active fiber fiber force Active fiber Lateral force transmission Types of muscle Skeletal muscles o Striated muscle attached to bones of the skeleton o Control body movement o Voluntary control; responds to somatic motor neurons Cardiac muscle o Striated muscle found only in the heart o Moves blood through the circulatory system o Involuntary control; responds to autonomic innervation, spontaneous contraction, modulated by the endocrine system Smooth muscle o Primary muscle of the internal organs and tubes o Influence the movement of material into, out of and within the body o Involuntary control; responds to autonomic innervation, spontaneous contraction, modulated by the endocrine system Comparison of three muscle types Skeletal Smooth Cardiac Appearance under Light Striated Smooth Striated Microscope Fiber Arrangement Sarcomeres No Sarcomeres Sarcomeres Attached to bones; a few Forms the walls of hollow Location sphincters close off hollow organs and tubes; some Heart muscle organs sphincters Multinucleate; large, Uninucleate; small spindle- Uninucleate; shorter Tissue Morphology cylindrical fibers shaped fibers branching fibers T-tubule and sarcoplasmic No t-tubules; sarcoplasmic T-tubule and sarcoplasmic Internal Structure reticulum (S R) reticulum reticulum Actin, myosin; troponin and Actin, myosin; troponin and Fiber Proteins Actin, myosin; tropomyosin tropomyosin tropomyosin Comparison of three muscle types Skeletal Smooth Cardiac Control Ca2+, troponin Ca2+, calmodulin Ca2+, troponin Fibers independent from Some fibers electrically Fibers electrically linked via another linked via gap junctions gap junctions Ca2+ from SR Ca2+ from ECF, SR Ca2+ from ECF, SR Contraction Speed Fastest Slowest Intermediate Contraction Force of Single Fiber Twitch Not graded Graded Graded Initiation of Contraction Requires ACh from motor Stretch, chemical signals. Autorhythmic neuron Can be autorhythmic Neural Control of Contraction Somatic motor neuron Autonomic neurons Autonomic neurons Hormonal Influence on Contraction None Multiple hormones Epinephrine Skeletal muscle anatomy Skeletal muscle anatomy T-tubule T-tubules (transverse-tubule) Holes: extracellular compartment Extensions of the cell membrane (sarcolemma) that associate with the ends (terminal cisternae) of the sarcoplasmic reticulum Carries action potential into deep portion of muscle fiber Sarcoplasmic reticulum Sarcoplasmic reticulum Ca2+ storage, release, reuptake Surrounds myofibrils Terminal cisternae Primary site of Ca2+ release Longitudinal SR Primary site of Ca2+ reuptake Triad Triad = T-tubule + 2 × Terminal cisternae Sarcoplasmic reticulum: key protein Dihydropiridine receptor (DHPR, Cav1.1) channel Ryanodine receptor (RyR) channel Sarcoplasmic reticulum: key protein Calsequesterin SR-Ca2+-ATPase In SR Actively pump Ca2+ into SR Ca2+ reservoir: Ca2+ binding protein Main determinants of muscle relaxation Influences opening of RyR Sarcomere Sarcomere Sarcomere Titin & nebulin  Fiber type Slow-Twitch Oxidative; Fast-Twitch Oxidative- Fast-Twitch Glycolytic; Red Muscle (Type I) Glycolytic; Red Muscle (Type IIA) White Muscle (Type IIB/IIX) Speed of Development of Slowest Intermediate Fastest Maximum Tension Myosin ATPase Activity Slow Fast Fast Diameter Small Medium Large Contraction Duration Longest Short Short Ca2+-ATPase activity in SR Moderate High High Endurance Fatigue resistant Fatigue resistant Easily fatigued Least used: jumping; quick, fine Use Most used: posture Standing, walking movements Glycolytic; more anaerobic than Glycolytic but becomes more Metabolism Oxidative; aerobic fast-twitch oxidative-glycolytic oxidative with endurance training type Capillary Density High Medium Low Mitochondria Much Moderate Few Color Dark red (myoglobin) Red Pale Fiber type Immunohistochemical Staining of Skeletal Muscle Staining myosin ATPase isoforms Type I fibers Type IIa fibers Type IIx fibers Dystrophin (protein in sarcolemma) Fiber type 2. Active contraction of skeletal muscle Motor unit Neuromuscular junction Motoneuron terminal Synaptic vesicles Ach Synaptic cleft Junctional folds: motor endplate Ach receptor clusters Ach reuptake: Ach-esterase Neuromuscular junction Excitation-contraction coupling Excitation-contraction coupling Excitation-contraction coupling Cross-bridge cycling: molecular level Crossbridge cycle Muscle contraction in order ( ) Signal from CNS ( ) Myosin head binding site exposed ( ) Ca2+ binds to Troponin C ( ) Tropomyosin conformational change ( ) Ach diffusion in synaptic cleft ( ) Ach binds to nicotinic receptor on membrane ( ) Voltage-gated Ca2+ channel open: Ach release ( ) Action potential reaches Triad (= + ) ( ) Nervous signal propagation through α motor neuron ( ) Voltage-gated Na+ channel open: Action potential propagation along sarcolemma ( ) Contraction ( ) Ca2+ leak from sarcoplasmic reticulum Muscle contraction in order 1. Signal from CNS 2. Nervous signal propagation through α motor neuron 3. Voltage-gated Ca2+ channel open: Ach release 4. Ach diffusion in synaptic cleft 5. Ach binds to nicotinic receptor on the sarcolemma (muscle fiber membrane) 6. Voltage-gated Na+ channel open: Action potential propagation along the sarcolemma 7. Action potential reaches Triad (= + ) 8. Ca2+ leak from sarcoplasmic reticulum 9. Ca2+ binds to Troponin C 10. Tropomyosin conformational change 11. Myosin head binding site exposed 12. Contraction Structure of skeletal muscle Fiber type Length-tension relationship Sliding filament theory Optimal length (Lo) Sarcomere length that elicits maximal force Maximal overlap of thick & thin filaments Force-pCa relationship Contractions Concentric Eccentric Isometric  Force × Velocity curve Force – Power relationship Muscle fiber composition Native myosin isoforms Power = Force × Velocity Vmax Myosin heavy chain isoforms [Watts] = [N] × [m/s] Myosin light chain isoforms Cross-sectional area of Po Muscle group Muscle Muscle fiber Myofibrillar protein Summation of contractions Summation of contractions 3. Smooth muscle Smooth muscle contraction Smooth muscle in blood vessel Blood vessel wall = smooth muscle + elastic/fibrous connective tissue Wall thickness varies in different vessels Autonomic effects on smooth muscles 4. Application Sources of ATP production in muscle ATP is required for muscle contraction as release of energy from ATP hydrolysis provides energy for power stroke. Myosin ATPase breaks down ATP as fiber contracts ATP → ADP + Pi Sources of ATP Phosphocreatine (PC) Glycolysis Oxidative phosphorylation Metabolism in muscle  Muscle twitch Definition : Draw a muscle twitch How do we stimulate muscle? Tension Time Single stimulus Muscle twitch & tetanic contraction Tension Time 1 Hz 5 Hz 10 Hz 20 Hz 100 Hz SUMMATION Sliding filament theory Muscle contraction requires overlapping of ( ) and ( ). Muscle fatigue Central fatigue due to CNS Peripheral fatigue due to neuron and muscle Extended submaximal exercise leads to depletion of glycogen storage Short-duration maximal exertion leads to Pi↑ May decrease Ca2+ release Maximal exercise leads to ion imbalances K+ leaves muscle fiber, leading to increased extracellular [K+], altering membrane potential Changes Na+-K+-ATPase activity Muscle fatigue Evidence supports failure of EC coupling for fatigue Lactate accumulation is no longer a likely cause of fatigue  Potential sites of muscle fatigue 1. Neuromuscular transmission 2. Sarcolemma excitability 3. Excitation-contraction coupling 4. Contractile apparatus 5. Metabolic energy supply and metabolite accumulation Proposed theories to explain exercise-related skeletal muscle cramps Muscle disorders Muscle cramp Sustained painful contraction Overuse Fatigue or soreness Disuse leads to atrophy Acquired disorders Inherited disorders Duchenne muscular dystrophy Absence of dystrophin McArdle’s disease Myophosphorylase deficiency Glycogen not converted to glucose 6-phosphate Duan (2021) Nat Rev Dis Primers Muscle disorders: rhabdomyolysis Symptoms Muscle tenderness Muscle aching (myalgia) or stiffness General weakness Reduced urine output Red or dark-colored urine Weakness of affected muscles Seizures Joint pain Fatigue Unintentional weight gain Causes Strenuous muscle exercise Occlusion of muscular vessels Trauma, compression Hyperthermia Infection Electrical shock Drug, toxins Metabolism abnormalities Electrolyte abnormalities  Muscle contractility in research How can we measure the muscle contractility? In vivo In vitro In situ  Muscle contractility in research How can we measure the muscle contractility? In vivo In vitro In situ