40-45% of the total body mass is muscle
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1 ANTERIOR AND POSTERIOR VIEW OF THE HUMAN MUSCULAR SYSTEM 40-45% of the total body mass is muscle FLEXION AND EXTENSION OF THE LOWER ARM origin tendon When the muscle contracts, the two bones are pulled toward each other. (exceptions: spincters, diaphragm, eye muscles, etc.) Muscle strength: 3-4kg/cm 2 Biceps brachii tendon FLEXION 10/2=5 area=r 2 Π 5*5*3.14 =78cm 2 78*3 = 234Kg??? EXTENSION Triceps brachii insertion 1
2 Bone Tendon Blood vessel CROSS SECTION OF A SKELETAL MUSCLE Muscle Epimysium (surrounding total muscle) Perimysium (surrounding fascicle) Muscle fascicle Muscle fiber (cell) Endomysium (surrounding fiber) CROSS SECTION OF A SKELETAL MUSCLE Epimysium (surrounding total muscle) Perimysium (surrounding fascicle) Blood vessels Muscle fascicle Muscle fiber (cell) Endomysium (surrounding fiber) 2
3 MICROSCOPIC IMAGE OF A STRIATED MUSCLE CELL anisotrop nucleus isotrop CROSS SECTION OF A MUSCLE FIBER Myofibril Sarcolemma T (transverse) tubule I band A band Z disc H zone Terminal cisternae I band Z disc Sarcoplasmic reticulum 3
4 The components of the skeletal muscle cell: (M) a) myocardium b) myofibrillum c) terminal cistern d) sarcolemma bcd SARCOMERE Thick filament MYOSIN Thin filament ACTIN Relaxation Contraction 4
5 Garlic string PRINCIPLE OF THE SLIDING-FILAMENT THEORY: The length of filaments does not change, but the distance between them. 5
6 In striated muscles, during contraction (S) a) ATP-ase activity of actin is stimulated by b) tropomyosin is attached to myosin c) heads of actin filaments are attached to myosin d) heads of myosin filaments are attached to actin d In the skeletal muscle, one of the proteins involved in the contraction has ATP-ase activity. This protein is (S) a) troponin C b) actin c) tropomyosin d) myosin e) troponin I d 6
7 TRIAD AND THE FATE OF CALCIUM sarcolemma action potential Ca-pump Rianodine receptor sarcoplasma terminal cistern Dihidropiridine receptor ped Transverse tubule calcium channel ATP How does disappear from the sarcoplasma? a) actively pumped back to the sarcoplasmic reticulum b) by Na-Ca exchange via cell membrane c) actively pumped out of the cell troponin In striated muscles during contraction, is released from (S) a) troponin b) transverse tubules c) terminal cisternae d) sarcomere c 7
8 What is the stimulus for the release of ions from the terminal cisterns in the skeletal muscle? (S) a) depolarization b) activation of troponin C c) calmodulin d) conformational change in tropomyosin e) activation of a Ca-ATP-ase f) activation of IP3/DAG system a During muscle contraction, ATP is used for TWO processes which are as follows (M) a) exposing the myosin-binding sites in the actin (moving the tropomyosin molecules) b) release of Ca ions from the terminal cisterns c) interaction between actin and myosin d) reaccumulation of Ca ions in the endoplasmic reticulum e) binding between troponin I and actin cd 8
9 CONSTRUCTION OF A THIN MYOFILAMENT Troponin I (Inhibition) Troponin C ( ) Troponin T (Tropomyosin) ACTIN TROPOMYOSIN Head-tail overlap Myosin walks on the surface of actin as a result of power stroke 9
10 Muscle innervation NEUROMUSCULAR JUNCTION A single motor neuron and the muscle fibers it innervates constitute a motor unit. 10
11 SARCOPLASMIC RETICULUM MUSCLE CELL In the neuromuscular synapsis, Ach acts on (S) a) Ach-gated channels selective for K + b) Ach-gated channels c) Ach-gated cation channels d) Na-K pump c 11
12 Excitation: Ach Nicotine Acetylcholine binding site pore Inhibition: Curare Succinyl-choline Extracellular space cell membrane M2 α-helix gate Intracellular space How does curare inhibit the neuromuscular junction? (S) a) it blocks the action of the Ach-esterase b) it binds to the Ach receptor in the postsynaptic membrane c) it blocks the spreading of the action potencial in the axon d) it inhibits the release of Ach e) it inhibits the voltage-dependent calcium channels of the presynaptic membrane b 12
13 Membrane depolarisers: venoms that open Na-channels Arrow poison frog Batrachotoxin Moray eel Ciguatoxin Rhododendron Grayanotoxin Membrane stabilisers: venoms that block Na-channels Fugu Tetrodotoxin Dinoflagellate Saxitoxin Blue ringed octopus Maculotoxin Synaptic venoms that disrupt vesicles and deplete ACh from nerve endings Funnel web spider Atraxotoxin Black widow spider Latrotoxin Taiwan banded krait Bungarotoxin Synaptic poison that prevents the release of ACh Clostridium botulinum Botulinum toxin 13
14 How does the tetrodotoxin inhibit muscle activity? (S) a) it blocks the action of the Ach-esterase b) it binds to the Ach receptor on the postsynaptic membrane's surface c) it blocks the spreading of the action potencial d) it inhibits the release of Ach c ENERGY SOURCES ATP phosphorylcreatine (ATP regeneration) carbohydrates- (aerob/anaerob-lactic acid) and FFAs FIBER TYPES IN MUSCLE white mucles (short twitch duration) red muscles (long, slow contractions and myoglobine) MUSCULAR ACTIVITY AND BODY RESPONSES Factors responsible for grading of muscular activity: a) number of cross-bridges b) recruitment of motor units c) tetanic stimulation (Ca) d) training (filaments) Oxygen debt mechanism Waste product transport Heat production/loss balace Fatigue ( stiffness ) HEAT PRODUCTION IN MUSCLE Resting heat basal metabolism Activation heat Ca-release Shortening heat cross-bridge formation Relaxation heat pumps Recovery heat reloading internal stores 14
15 MYOGRAMS OF SEVERAL TYPES OF CONTRACTIONS Tension Latent period Contraction Relaxation action potential A B C D stimulus Twitch Summation Incomplete tetanus Complete tetanus Time LENGTH-TENSION TENSION RELATIONSHIP FOR MUSCLE FIBER Relative tension (%) 150 Total tension 100 Passive tension 50 Active (isometric) tension Sarcomere length (µm) 15
16 TYPES OF CONTRACTION contractile part serial visco-elastic element movement parallel visco-elastic element fixation point Isometric Isotonic Auxotonic During isotonic contraction: (S) a) neither the length of the muscle nor the strain changes b) the strain increases, the length does not change c) the strain increases, the length decreases d) the strain does not change, the length decreases e) the strain decreases, the length does not change d The definition of isometric contraction: (S) a) neither the length of the muscle nor the strain changes b) the strain increases, the length does not change c) the strain increases, the length decreases d) the strain does not change, the length decreases e) the strain decreases, the length does not change b 16
17 Isometric contraction: (M) a) tension increases but the length of the muscle does not change b) the muscle shortens but the tension does not change c) isometric contraction occurs in the muscles of the arm when we hold a cup of tea d) isometric contraction occurs in the muscles of the are when we lift a cup of tea ac DIFFERENT MUSCLE TYPES UNDER MICROSCOPE striated (skeletal) muscle smooth muscle cardiac muscle 17
18 a) Skeletal muscle b) Smooth muscle Muscle fiber (cell) Muscle cell Myofibril Membrane Dense bodies hexagonal arrangement Nucleus Sarcomer random arrangement Thick filaments Gap junction Thin filaments I band H zone A band Z disc DIFFERENCES AND SIMILARITIES SKELETAL MUSCLE striated under microscope voluntary contracts by nerve stimulus there are no junctions between cells SMOOTH MUSCLE smooth under microscope involuntary contracts by nerve OR chemical OR mechanical stimulus there are gap junctions between cells Contractile elements AKTIN MYOSIN (heavy/light chain) Regulatory proteins Troponin Phosphatase Structural proteins Aktinin Dezmin Vimentin Contractile elements AKTIN MYOSIN (heavy/light chain) Regulatory proteins Calmoduline MLCK (Myosine light chain kinase) Phosphatase Structural proteins Aktinin Dezmin Vimentin 18
19 Molecular structure of smooth muscle tropomyosin caldesmon calponin actin essential light chain regulatory light chain myosin THE MECHANISM OF SMOOTH MUSCLE CELL CONTRACTION Voltage gated Ca channel IP 3 receptor 19
20 Calcium for smooth muscle contraction caused by neural stimulation is derived from (S) a) extracellular space (in part) b) mitochondria c) terminal cisternae d) it is released from protein-binding a Which protein is phosphorylated in the smooth muscle prior to contraction? (S) a) actin b) myosin c) calmodulin d) troponin e) tropomyosin b 20
21 ENDOTHELIUM-DERIVED RELAXING FACTOR (EDRF) Acetylcholine Acetylcholine Vascular smooth muscle (endothelial cells are removed) Endothelial lining is intact Contraction Relaxation THE MOST POTENT EDRF: NITRIC OXIDE Receptor G q α Calmodulin Arg NOS PLC IP3 Ca Citrulline + NO NO PKG Ca decrease Guanylylcyclase GTP cgmp Phosphodiesterase Inactivation Sidenafil citrate RELAXATION L-NAME Endothelial cell Smooth muscle 21
22 NO NOS: NOS-1 (nnos): neural NOS-2 (inos): phagocytes (cytokine-induced NOS) NOS-3 (constitutional): endothelial cells NO is stimulated by: acetylcholine histamine (H1) bradykinin VIP (vasoactive intestinal peptide) SP (substance P) NA (NO dcereases NA-induced vasoconstriction) sheer stress LOCALLY ACTING VASOACTIVE SUBSTANCES Smooth muscle Endothelial cell ET-A IP3/Ca TP 5HT2a Endothelin-1 Contraction B1 TXA2 NK2 M1 Serotonin 5HT2a α1 Bradykinin B1 H1 Neurokinin A NK2 NK1 Contraction Acetylcholine M1 α2 Noradrenaline α1 camp A1 Histamine H1 Substance P NK1 H2 CGRP? Relaxation? VIP?? A2 Adenosine PGE2 camp EP1-4 IP PGI2 NO IP3/Ca NO 22
23 NERVE Single-unit (visceral) smooth muscle Smooth muscle cell Multi-unit smooth muscle RELAXATION CONTRACTION CONTRACTION Multi-unit: Single-unit: (visceral) nervous system myogene nervous system humoral Synaptic knob Synaptic vesicles 1. Action potentials arrive at synaptic knob 2. Calcium ions diffuse into synaptic knob 3. Synaptic vesicles release acethylcholyne (ACh) 4. ACh binds to receptors on the sarcolemma 5. Ion channels in ACh receptor opens. Na + enters and K + leaves sarcoplasm through the same channel, creating the end-plate potential (EPP) 23
24 6. EPP excites voltagegated ion chennels in adjacent regions of sarcolemma. Diffusion of Na + and K + through their separate channels depolarizes membrane and initiates action potential in muscle fiber. 7. Action potentials propagated down T tubules to interior of muscle fiber. 8. Terminal cisternae of sarcoplasmic reticulum release a flood of into the sarcoplasm. 9. Calcium ions bind to troponin C. 10. Troponin-tropomyosin complexes shift position, exposing active sites where actin will subsequently bind to myosin. Troponin Tropomyosin active sites myosin Activation 11. An ATP molecule bound to the myosin head is hydrolyzed to ADP and P i which remain bound to the myosin. Cross-bridge formation Power stroke 12. Activated myosin is now able to bind to the active site of an actin monomer. 13. Myosin releases ADP and P i. The head flexes and pulls the thin filament along the thick filament. 24
25 14. Myosin remains flexed and bound to the actin until another ATP molecule binds to it. 15. Binding of a new ATP molecule causes myosin to release actin and return to the forward position, ready to repeat the cycle. 16. Signals stop arriving from motor neuron. 17. Acethylcholine (ACh) release ceases. 18. ACh dissociates from receptors on sarcolemma. 20. Calcium ions are transported back into sarcoplasmic reticulum. 19. Free ACh is broken down by acethylcholinesterase (AChE). ACh fragments are reabsorbed by synaptic knob. Muscle stimulation ceases. 21. Calcium ions dissociate from troponin. 22. Troponin blocks active sites of actin, preventing actin-myosin cross bridges from forming. 25
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