Muscles - PHA106 Pharmaceutical Biosciences 1 PDF

PHA106 Pharmaceutical Biosciences 1 MUSCLES  Learning outcomes  Understanding of the functions & features of skeletal muscle  Knowledge of sarcomere and events involved in muscle contraction  Understanding of muscle stimulation  Muscle types  Ske...

PHA106 Pharmaceutical Biosciences 1 MUSCLES  Learning outcomes  Understanding of the functions & features of skeletal muscle  Knowledge of sarcomere and events involved in muscle contraction  Understanding of muscle stimulation  Muscle types  Skeletal – muscles, movement  Cardiac - heart, pumping of blood  Smooth – gastrointestinal tract and small arteries  Skeletal muscle  6 main functions  Produce skeletal movement  Maintain posture & body position  Support soft tissues  Guard body entrances & exits  Maintain body temperature  Store nutrients Distinctive features of skeletal muscle  Myocytes are large, tubular cells  Multinucleate  Cells are banded or striated  Sarcolemma  Sarcoplasm  Transverse or T tubules  Continuous with the sarcolemma  Extend deep into sarcoplasm  When action potential depolarises sarcolemma this impulse is transferred to rest of fibre via T tubules Distinctive features of skeletal muscle  Myocytes contain many chains of myofibril  Shortening of myofibrils produces contractions  Myofibrils are composed of myofilaments  Thin filaments made of actin  Thick filaments made of myosin  Elastic filaments made of titin  Myofibrils anchored to sarcolemma  Sarcoplasmic reticulum Cross-section of a myocyte Distinctive features of skeletal muscle  Sarcomeres – give the striated appearance to muscles  Basic unit of skeletal muscle  Repeating units of myofilaments  Contain thick filaments (myosin), thin filaments (actin), stabilising proteins, regulatory proteins  Banding due to distribution of thick and thin filaments  A bands - M line, H zone, zone of overlap  I bands - Z line  Titin extends from ends of thick filaments to Z line M line  1 2 6 7 3 4 8 9 5  Events at the neuromuscular junction  Neuron axon terminal meets muscle fibre at NMJ  Action potential reaches presynaptic neuron terminal  Voltage gated Ca channels open – influx of Ca ions  Causes ACh-containing vesicles to bind to presynaptic membrane  ACh released across synapse  Binds to AChR on muscle fibre, ligand-gated Na ion channel  Influx of Na ions produces action potential in sarcolemma  AChE removes ACh  Muscle contraction  Action potential travels down sarcolemma and T tubules  Ca2+ ions released from SR - bind to thin filament causing a change in its conformation  Thick filaments composed of ~300 myosin molecules  ATP binds to myosin head and is hydrolysed to ADP & P  Activated mysoin head forms cross bridge with actin  ADP & P are released and myosin head pivots  Slides thin filament towards centre of sarcomere  ATP binds to myosin which detaches from thin filament  Sliding filament theory  Sliding filament theory https://www.youtube.com/watch? v=gZevEd0qeW4  Frequency of muscle stimulation  Twitch – single stimulation or contraction  Latent period  Contraction phase  Relaxation phase  Treppe  Wave summation  Incomplete tetanus  Complete tetanus Myogram of single muscle twitch  Type of muscle contractions Isotonic contractions  Tension remains constant, muscle length changes  Walking, running, lifting an light object  Skeletal muscle obeys ‘all or none’ law  Type of muscle contractions Isometric contractions  Tension increases, muscle length remains constant  Tension produced cannot exceed load  Carrying a heavy object  Muscle energy  ATP stores are not sufficient to maintain muscle contraction  ATP is generated at the same rate it is used  At rest, ATP transfers energy to creatine to produce phosphocreatine  During contraction, myosin breaks down ATP to ADP & P, phosphocreatine is then used to ‘recharge’ the ADP concerting it to ATP  Creatine kinase is the enzyme involved  Muscle damage results in high blood CK levels  Muscle fatigue  Depletion of metabolic reserves  Lactic acid build up  Decrease in pH within muscle fibres which decreases Ca binding to thin filaments  Cumulative  Myasthenia gravis  Autoimmune disease of the NMJ  Antibodies damage AChR on skeletal muscle fibres  ACh is released but there are insufficient receptors to bind to  Action potential is not propagated down muscle fibre  Muscle weakness/fatigue  Treat with AChE inhibitor  Summary  Understanding of the functions & features of skeletal muscle  Knowledge of sarcomere and events involved in muscle contraction  Understanding of muscle stimulation  Additional reading Martini 11th edn. Chapter 10 & 11