Muscles 2
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  • Muscle as a tissue
  • Muscle fibers = skeletal muscle The last bullet was something she mentioned in the lecture Talked about slide 5, 6 SLIDE 4
  • 3 rd organ system  muscular system Composed mainly of muscles (organs) Skeletal muscle (organ) Composed of a) skeletal muscle tissue – main component b) connective tissue c) blood vessels d) lymphatic vessels e) nerve fibers Arrangement of skeletal muscle fibers inside the skeletal muscle tissue (which are inside the skeletal muscle) Each skeletal muscle fiber (cell) is wrapped in a delicate connective tissue membrane called the ENDOMYSIUM A group of endomysium-covered skeletal muscle fibers forms a FASCICLE  wrapped by CT membrane called the Perimysium A bundle of perimysium-covered fascicles forms skeletal muscle  wrapped in a coarse CT membrane called epimysium Went to slide 9
  • Blood vessels, nerve fibers, etc to form the organ, Then wrote down bullets on slide 3
  • Went back to slide 2
  • Attachment sites for skeletal muscles  attachment may be DIRECT OR INDIRECT  via tendons Most of the skeletal muscle in the body are attached to bones (or cartilage) indirectly 2 advantages to indirect attachment of skeletal muscles: The rope-like tendons can fit into small spaces to reach the bones Skeletal muscles that course over joints will be protected if tendons run directly over the joint sites  skeletal muscles will be damaged at the joint sites as the joints move
  • Microscopic arrangement of the skeletal muscle fiber  because this explains the mechanism of skeletal muscle contraction Each skeletal muscle (the organ) consists of skeletal muscle fibers that run the entire length of the skeletal muscle Each skeletal muscle fiber  80% of volume occupied by rod-like structures called MYOFIBRILS (run the entire length of skeletal muscle fibers) MYOFIBRILS are composed of smaller filaments called MYOFILAMENTS 2 types of myofilaments thick filament – thicker than the thin filament thin
  • 2 types of myofilaments thick filament – thicker than the thin filament; composed of structural proteins called myosin structure of a myosin molecule  a rod-like tail that ends in 2 globular heads  MYOSIN HEADS myosin heads have a binding site for ACTIN; also has binding site for enzyme ATPase that hydrolyzes ATP  ADP + Pi; myosin head itself can act as an ATPase THICK FILAMENTS consists of 300 molecules of myosin molecules arranged such that the tails form the core with the heads exposed thin - composed of 3 types of proteins (actin, tropomyosin, troponin) actin – double helical structure that forms the core of the thin filament; contains binding sites for MYOSIN (binding sites on actin bind to the actin binding sites on myosin) tropomyosin – in a relaxed skeletal muscle (not contracted), tropomyosin spirals about the actin blocking myosin binding sites on actin troponin – a three-complex protein that consists of: 1) troponin C  binds calcium ions 2) troponin subunit that binds to tropomosin (TnT) 3) troponin subunit that binds to actin and inhibits actin  inhibitory troponin (TnI)
  • In a skeletal muscle fiber, the thick and the thin filaments are arranged in an alternating pattern THICK, THIN, THICK, THIN and so on Which explains the straited appearance of skeletal muscles The thin filaments are anchored/stabilized by proteins called the Z disc or Z lines The distance between 2 successive Z lines is referred to as a SARCOMERE  structural unit of skeletal muscle Shortening of sarcomeres results in skeletal muscle contraction ======================== Components of a sarcomere distance between two z-lines z lines anchor the thin filaments in a sarcomere we know the thin and thick filaments alternate in a sarcomere thick filament is referred to as the “A BAND” in a sarcomere the regions of the thin filaments not overlapping with the A band are called the I bands the region of the A band not overlapping with the thin filaments is called the H zone the line bisecting the H zone is called M line  anchors the A band in a sarcomere I band are located toward the Z lines The H zone is located in the central region of the A band
  • Sliding fillament mechanism of the skeletal muscle contraction Sliding of the thin filament in sarcomeres toward the M line in the H zones causes shortening of sarcomeres as the Z lines are pulled inward Since sarcomeres run the entire length of the myofibrils, the myofibrils also shorten Since the myofibrils run the entire length of skeletal muscle fibers, the fibers also shorten Since skeletal muscle fibers run the entire length of the skeletal muscle, the organ (skeletal muscle) ALSO SHORTENS.
  • 10-18 started here
  • Factors that affect the strength of skeletal muscle contraction  force developed by the skeletal muscle Size of the motor units activated Number of motor units activated when we’re looking at recruitment FREQUENCY of skeletal muscle activation  If action potentials are developed at a higher rate such that the skeletal muscle fibers do not have time to sequester calcium ions into the SR  more and more calcium ions remain in the sarcoplasm resulting in stronger and stronger skeletal muscle contraction  this effect is referred to as TEMPORAL (time) or WAVE SUMMATION Slide 35 after slide 34
  • Drew a graph of strength of skeletal muscle contraction vs. frequency of activation where both increase until a plateau is reached When the skeletal muscle contraction levels off it is called TETANY The response in contraction of a motor unit to a single action potential is what is referred to as a TWITCH
  • 4) (from slide 33) Length of the sarcomere before contraction begins… The optimum length of sarcomeres = 2.0 microns – 2.25 microns At these lengths  MAXIMUM contraction of the skeletal muscle because  H zone is present and the activated myosin heads can reach/bind to their sites on actin to initiate sliding of the thin filament into the H zone that is available Sarcomere lengths below the optimum (less than 2.0 micron)… The H zone present is decreased  hence, sliding of thin filaments is reduced (impeded) = less sliding of the thin filaments  less shortening of the sarcomeres  less contraction of the skeletal muscle  less force generated Sarcomere lengths above the optimum (more than 2.25 micron) Ample space in the H zone; however there is little or NO overlap between the A band and the thin filaments. Hence, the activated myosin heads can NOT reach and bind to their sites on actin  NO SLIDING of the thin filaments  NO SHORTENING OF SARCOMERES WILL OCCUR  NO CONTRACTION of skeletal muscle  no force generated
  • Sources of ATP to support skeletal muscle contraction Stored ATP in skeletal muscle fibers  stored ATP can support ONLY 5 seconds of skeletal muscle activity Creatin phosphate (CP) = unique in muscle cells (especially in skeletal muscle fibers) CP  phosphorylates ADP to give ATP (ADP + CP  ATP + Creatine **where creatine kinase is over the arrow as an enzyme) 3) Catabolism (break down) of glucose in the absence of oxygen is referred to as ANAEROBIC CATABOLISM of glucose (Glycolysis) The anaerobic catabolism of glucose (anaerobic respiration) yields 2 molecules of ATP and pyruvic acid (when O2 absent, pyruvic acid  Lactic acid  contributes to MUSCLE FATIGUE  halts skeletal muscle contraction 4) AEROBIC CATABOLISM OF GLUCOSE (with O2)  36 – 38 molecules of ATP; more efficient in generating ATP to support muscle contraction, BUT it involves MORE steps then anaerobic catabolism of glucose
  • Based on the table in the book s SLOW oxidative fibers also called RED fibers Fast glycolytic fibers are also called WHITE FIBERS Activities the 3 types of skeletal muscle fibers are suited for Slow oxidative fibers  use aerobic respiration to generate ATP hence, they are fatigue-resistant and suited for endurance-type activities A successful marathon runner possesses more of the slow oxidative fibers Fast oxidative fibers are intermediate fibers that are more efficient and fatigue-resistant compared to glycolytic fibers however, they are less efficient when compared to the slow oxidative fibers Hence, you use fast oxidative fibers in medium length activities such as walking, standing Fast glycolytic fibers  largest, use anaerobic respiration. Hence, lactic acid builds up, causing muscle fatigue fatigable so they are suited for intense but short-lived activities such as weight lifting
  • Matured skeletal muscle grows by HYPERTROPHY  increase in the size of the skeletal muscle fibers (which are actually cells) in the skeletal muscle Skeletal muscle fibers are MULTINUCLEATE cells and therefore, they lose the ability to undergo mitosis which would have resulted in hyperplasia As skeletal muscle grows by hypertrophy, the larger skeletal muscle generates MORE FORCE = “the bigger the skeletal muscle, the greater the force it generates” Skeletal muscle NOT activated or used will undergo muscle atrophy (DECREASE in skeletal muscle size)  decrease the force generated by the skeletal muscle
  • Usually found lining tracts in the body (tracts = opening to the exterior) No striations
  • No troponin, z discs absent, no sarcomeres Skeletal muscle fiber (drew T tubule and terminal cisternae) Smooth Muscle cell (shallow dips called caveolae instead of T tubules)
  • Excitation-contraction coupling of smooth muscle cells Smooth muscle cells may be activated to contract or inhibited from contracting resulting in RELAXATION Smooth muscle cells are innervated by the AUTONOMIC NERVOUS SYSTEM Sympathetic Nervous System Parasympathetic Nervous system Typically, activation of the sympathetic nervous system will result in smooth muscle contraction (exception: in the bronchioles in the lungs, activation of the sympathetic nervous system actually results in relaxation of the smooth muscle  BRONCHODILATION) The autonomic fibers innervating the smooth muscle cells form DIFFUSE JUNCTIONS  wide spaces between the smooth muscle cells and the ends of the autonomic fibers  the ends of the autonomic fibers appear bulbous  referred to as VARICOSITIES. HENCE a diffuse junction forms between the sarcolemma of the smooth muscle cell and a varicosity of an autonomic fiber Activation of the parasympathetic nervous system will result in RELAXATION of the smooth muscle. 3) Unlike skeletal muscle, smooth muscle can be activated to contract or relax by blood-borne chemicals such as hormones 4) Some smooth muscle cells have intrinsic cells that depolarize spontaneously to stimulate smooth muscle contraction  these cells are called PACEMAKER cells Hence, the smooth muscle has the INTRINSIC ability to contract = pacemaker activity THREE WAYS TO CONTRACT SMOOTH MUSCLE (she went to 45)
  • SEQUENCE OF EVENTS When smooth muscle is activated to contract by the sympathetic nervous system/chemical/pacemaker activity, depolarization of the sarcolemma causes calcium channels in the sarcolemma to open up and these channels will allow calcium ions in the fluid inside the caveolae to enter into the sarcoplasm of the smooth muscle cell. Entry of calcium ions into the sarcolemma triggers more calcium ions to be released from the poorly developed SR in the smooth muscle cells (TRIADS ARE ABSENT) ** because calcium ions must enter from the extracellular fluid, calcium channel blockers reduce or abolish smooth muscle contraction Since troponin is absent in smooth muscle cells, the increased calcium ions bind to a regulatory protein in the sarcoplasm called CALMODULIN ============== 10/27/10 Excitation-Contraction Coupling in smooth muscle cell step 1: Sarcolemma is depolarized by the pacemaker activity or autonomic fiber activation or by chemicals in blood. step 2: Calcium channels open up in the sarcolemma and Ca+ ions enter the cell from the extracellular fluid in the caveolae. Hence, calcium channel blockers can inhibit smooth muscle contraction Ca+ ions are also released from the SR in the smooth muscle cell **calcium ions to support or initiate smooth muscle contraction come from 2 sources a) extracellular fluid b) from the SR step 3: Calcium ions bind to calmodulin to form Calcium-calmodulin complex step 4: calcium calmodulin complex activates a kinase called MYOSIN LIGHT CHAIN kinase (MLCK) step 5: activated MLCK attaches phosphate to the myosin heads  results in activation of the myosin heads step 6: activated myosin heads bind to their sites on actin (in a smooth muscle cell the myosin binding sites on actin are ALWAYS accessible; although tropomysoin is present, it does NOT block myosin binding sites on actin) step 7: the attached activated myosin heads form CROSSBRIDGES and as the phosphate dissociate from the crossbridge, the crossbridge undergoes a change in orientation termed the POWER STROKE which causes the thin filaments to slide downward along the axis of the smooth muscle  results in contraction of the smooth muscle step 8: cross bridge detachment is caused by the enzyme PHOSPHORYLASE To cause complete relaxion of the smooth muscle Phosphorylase to cause crossbridge detachment Calcium ions are pumped (active transport) into the SR and out into the extracellular fluid Turn off the pacemaker activity or turn off the hormone released or stop activation of the autonomic nervous system  sympathetic nervous system **Activation of the autonomic nervous system may cause smooth muscle relaxation or smooth muscle contraction. In contrast, activation of the motor nuerons ALWAYS cause skeletal muscle contraction
  • 202 material - Cardiac Muscle Striated  have sarcomeres Highly branchedwith lateral contacts called INTERCALATED DISCS  2 parts Desmosomes and Gap Junctions Cardiac muscle is located in the wall of the heart in the middle layer of the heart wall called the myocardium If you look at the excitation-contraction coupling of cardiac muscle, it is similar to smooth muscle 1) Pacemaker activity 2) Autonomic Nervous system 3) Chemicals In addition, calcium ions enter the cardiac cells to trigger release of more Ca+ from the SR in the cardiac muscle cells Cardiac muscle  similar to skeletal muscle structurally, but similar to smooth muscle in terms of FUNCTION

Muscles 2 Presentation Transcript

  • 1. THE MUSCULAR SYSTEM
  • 2. 3 Types of muscle Tissue
    • Skeletal muscle tissue
    • striations; long, cylindrical cells called muscle fibers;
    • multinucleate cells
    • Cardiac muscle tissue
    • striations; branching cells form junctions called
    • intercalated discs;
    • uninucleate cells
    • Smooth muscle tissue
    • No striations; spindle-shaped cells;
    • uninucleate cells
    • Each muscle tissue type with connective tissue wrappings, blood vessels, nerve fibers = muscle as an organ
  • 3. Figure 9.2: Connective tissue sheaths of skeletal muscle, an organ (b) (a) Bone Perimysium Endomysium Blood vessel Muscle fiber (cell) Fascicle (wrapped by perimysium) Endomysium (between fibers) Epimysium Tendon Epimysium Muscle fiber in middle of a fascicle Perimysium Blood vessel Endomysium
  • 4. Skeletal Muscle (organ)
    • Each muscle fiber ( = skeletal muscle cell) is wrapped in a delicate CT membrane called ENDOMYSIUM
    • Fascicle – consists of a group of endomysium-covered muscle fibers wrapped in a coarse CT membrane called PERIMYSIUM
    • Skeletal muscle – consists of a group of fascicles wrapped in a tough CT membrane called EPIMYSIUM
  • 5. Patterns of Arrangement of Fascicles in skeletal Muscles
    • Muscle fibers in a skeletal muscle form bundles called fascicles . The muscle fibers in a single fascicle are parallel, but the organization of fascicles in the skeletal muscle can vary, as can the relationship between the fascicles and the associated tendon. The different patterns of fascicle organization form parallel muscles, convergent muscles, pennate muscles, circular muscles
    • Parallel Muscles In a parallel muscle, the fascicles are parallel to the long axis of the muscle. Most of the skeletal muscles in the body are parallel muscles. The biceps brachii muscle is a parallel muscle with a central body. When a parallel muscle contracts, it gets shorter and larger in diameter. A skeletal muscle cell can contract until it has shortened by roughly 30-50 percent. Because the fibers in a parallel muscle are parallel to the long axis of the muscle, when the fibers contract together, the entire muscle shortens by the same amount. If the muscle is 10 cm long, the end of the tendon will move 3-5 cm when the muscle contracts. Source: IFBB.com
  • 6. Pattern of Arrangement, continued
    • Convergent Muscles In a convergent muscle, the muscle fibers are spread over a broad area, but all the fibers converge at one common attachment site. The muscle fibers typically spread out, like a fan or a broad triangle, with a tendon at the apex. The pectoralis major muscle is a good example of it. A convergent muscle has versatility, because the stimulation of only one portion of the muscle can change the direction of pull. Then, convergent muscle fibers pull in different directions rather than all pulling in one same direction. Pennate Muscles In a pennate muscle, the fascicles form a common angle with the tendon. Because the muscle cells pull at an angle, contracting pennate muscles do not move their tendons as far as parallel muscles do. But a pennate muscle contains more muscle fibers--and, as a result, produces more tension--than does a parallel muscle of the same size. If all the muscle fibers are on the same side of the tendon, the pennate muscle is unipennate. More commonly, a pennate muscle has fibers on both sides of the tendon. Such a muscle is called bipennate. The rectus femoris muscle, for example, is bipennate If the tendon branches within a pennate muscle, the muscle is said to be multipennate. The triangular deltoid muscle of the shoulder is multipennate.
    • Circular Muscles also referred to as sphincters
    • the fascicles are arranged in concentric rings; they surround external body openings
    • Source: IFBB.com
  • 7. Patterns of Arrangements of Fascicles in skeletal Muscles Circular arrangement – the orbicularis oris and orbicularis oculi - muscles around the mouth and eyes, respectively
  • 8. Attachment sites for each skeletal muscle Skeletal muscles span joints and they have at least 2 attachment sites – the ORIGIN and the INSERTION The bone that moves (the movable bone) when the skeletal muscle contracts is known as the INSERTION; and the bone that does not move ( the immovable bone) is the ORIGIN . Hence, when the skeletal muscle contracts, the insertion moves toward the origin. Example: Brachioradialis Origin (O) - lateral supracondylar ridge at distal end of the humerus Insertion(I) – base of styloid process of radius Refer to tables in the lab manual and in the textbook ( pages 329-379)
  • 9. Direct Skeletal Muscle Attachments DIRECT ATTACMENTS - the epimysium of the skeletal Muscle is fused directly to the periosteum
  • 10. Naming of Skeletal Muscles
    • 1. Location of the muscle – name indicates region of the body its found in or bone its attached to. Example: Frontalis
    • 2. Shape of the muscle. Example Deltoid – roughly triangular
    • 3. Relative size – maximus (largest) – Gluteus maximus; longus (long)- palmaris longus
    • 4. Direction of muscle fibers/fascicles in reference to the midline of the body or the longitudinal axis of a limb bone. Examples: rectus ( straight)- rectus abdominis; transversus ( right angle) – transversus abdominis
    • 5. Number of origins/heads– biceps ( 2 origins) – biceps brachii; triceps
        • ( 3 origins/heads)-triceps brachii; quadrceps (4 heads) – quadriceps femoris
    • 6. Location of the attachments – their points of origin and insertion and the first part of the name indicated the origin. Example: sternocleidomastoid – origin is the sternum and the clavicle is the insertion point
    • 7. Action – the name indicates the movement the muscle produces. Example:
    • adductor – adductor longus for adduction of the thigh
    • Some muscles are named using more than one of the above criteria
  • 11. Figure 9.2a: Connective tissue sheaths of skeletal muscle, p. 283. (a) Bone Perimysium Endomysium Blood vessel Muscle fiber (cell) Fascicle (wrapped by perimysium) Endomysium (between fibers) Epimysium Tendon INDIRECT ATTACHMENT- the Connective tissue wrappings of the skeletal muscle extends as a tendon or an aponeurosis to anchor the muscle to bone, cartilage or fascia
  • 12. Figure 9.3a-c : Microscopic anatomy of a skeletal muscle fiber , p. 285. Nuclei Fiber Nucleus Light I band Dark A band Sarcolemma Mitochondrion H zone (b) Myofibril (a) (c) Thin (actin) filament Thick (myosin) filament Z disc Z disc
  • 13. Microscopic Anatomy of Skeletal Muscle Fiber
    • Each muscle fiber contains:
    • Myofibrils – rod-like structures that run the entire length of the muscle fiber; 80% of the volume of the muscle fiber is occupied by the myofibrils
    • Myoglobin – a red pigment that binds and stores oxygen
    • Inclusions - glycosomes contain glycogen
    • Mitochondria – for aerobic respiration to produce energy
    • Sarcoplasm – cytoplasm of the muscle fiber
    • Sarcoplasmic reticulum(SR ) – specialized smooth endoplasmic reticulum that stores/releases calcium into the sarcoplasm; the expanded ends of SR are called TERMINAL CISTERNAE
    • Sarcolemma – plasma membrane of muscle fiber
    • Transverse tubules(T-tubules) – involutions of the sarcolemma into the sarcoplasm
  • 14. Triad
    • Composed of a transverse tubule in between 2 terminal cisternae:
    • Terminal cisterna- Ttubule -Terminal cisterna
    • Function: for the release of calcium ions into the sarcoplasm when the sarcolemma depolarizes
  • 15. Figure 9.5: Relationship of the sarcoplasmic reticulum and T tubules to myofibrils of skeletal muscle, p. 288. Myofibril Myofibrils Triad Tubules of sarcoplasmic reticulum Sarcolemma Sarcolemma Mitochondrion I band I band A band H zone Z disc Z disc Part of a skeletal muscle fiber (cell) T tubule Terminal cisterna of the sarcoplasmic reticulum M line
  • 16. The Myofilaments
    • Each myofibril contains smaller structures called MYOFILAMENTS – 2 main types: MYOSIN and ACTIN
    • Thick filaments – 16nm in diameter; composed of the protein MYOSIN – 300 myosin molecules form a dark band called the A band
    • Each myosin consists of a tail and 2 globular heads .
    • The myosin globular heads have binding sites for actin, binding sites for ATP and contains the enzyme ATPase
    • Thin filaments – 8nm in diameter; anchored by the Z lines; Thin filaments contain 3 different proteins :
    • Actin – contains the binding sites for the myosin heads
    • Tropomyosin – a rod-shaped regulatory protein that spirals around the actin and blocks myosin binding sites on actin in a relaxed skeletal muscle
    • Troponin – a three-polypeptide complex namely
    • TnC – binds calcium ions
    • TnT – binds to tropomyosin
    • TnI - inhibitory subunit that binds to actin
    • Elastic filaments are composed of the protein tictin - they extend from Z lines through the A bands to attach to the M line thus, anchoring the A bands in place within the sarcomere
    300 myosin
  • 17. Figure 9.4: Composition of thick and thin filaments, p. 286. (b) (c) (d) (e) (a) Heads Flexible hinge region Tail Myosin head Troponin complex Tropomyosin Actin Thin filament Thick filament Thin filament (actin) Thick filament (myosin) Myosin heads Myosin molecule Portion of a thick filament Portion of a thin filament Longitudinal section of filaments within one sarcomere of a myofibril Transmission electron micrograph of part of a sarcomere
  • 18. Figure 9.11: Role of ionic calcium in the contraction mechanism, p. 294. (a) (b) (c) (d) Actin Actin Tnl TnT Tropomyosin Myosin binding sites Troponin complex TnC Myosin head Myosin binding site Additional calcium ions bind Additional calcium ions bind to TnC Myosin head Actin Overview Troponin Tropomyosin Myosin head Plane of (a) Plane of (d) + Ca 2+
  • 19. Sarcomeres
    • Structural units of skeletal muscle = each skeletal muscle is composed of repeated units arranged end to end called sarcomeres
    • The distance between 2 successive Z lines = a sarcomere
    • Components of a Sarcomere:
    • A band = thick filament
    • M line = line that bisects and anchors the A bands
    • Thin filaments alternating with “A” bands; the alternating pattern of the thick and thin filaments results in the characteristic striated appearance of skeletal muscle
    • Z lines (= Z discs) – anchor the thin filaments
    • H zone – middle region of the A band not overlapping with the thin filaments
    • I bands – regions of the thin filaments not overlapping with the A band
    Z M Z
  • 20. Figure 9.3c-e: Microscopic anatomy of a skeletal muscle fiber, p. 285. I band Z disc Z disc I band A band H zone (c) (d) (e) Thin (actin) filament Thick (myosin) filament Thin (actin) filament Elastic (titin) filaments Z disc Z disc M line M line Sarcomere Thick (myosin) filament I band thin filaments only H zone thick filaments only M line thick filaments linked by accessory proteins Outer edge of A band thick and thin filaments overlap
  • 21. The sliding Filament Mechanism of Muscle Contraction
    • States that the sliding of the thin filaments past the A bands results in muscle contraction
    • According to this mechanism when a muscle contracts there is more overlap between the thin filaments and the A bands:
    • H zone decreases or disappears
    • I bands decrease or disappear
    • Sarcomere length shortens = Skeletal muscle shortens ( contracts)
    • However, the lengths of the A bands and the thin filaments remain the same – they do not shorten
    1 2 3
  • 22. Figure 9.6: Sliding filament model of contraction , p. 289. A Z Z I I A Z Z A Z Z H 1 2 3
  • 23. Excitation-Contraction Coupling
    • What stimulates skeletal muscles to contract? When they are stimulated by activated MOTOR NEURONS
    • Motor neurons conduct impulses to skeletal muscles.
    • Motor neuron makes contact with skeletal muscle fibers via its AXONAL TERMINALS
    • Each axonal terminal innervates one muscle fiber in the skeletal muscle to form the NEUROMUSCULAR JUNCTION
    • The motor neuron and all the skeletal muscle fibers it
    • innervates via its axonal terminals is called a MOTOR UNIT
  • 24. Figure 9.7a: The neuromuscular junction, p. 290. (a) Action potential Axon terminal at neuromuscular junction Sarcolemma of the muscle fiber Nucleus Myelinated axon of motor neuron
  • 25. Figure 9.7: The neuromuscular junction, p. 290. (a) (b) (c) Axon terminal of a motor neuron Junctional folds of the sarcolemma at motor end plate Part of a myofibril Mitochondrion Synaptic cleft T tubule Binding of Ach to receptor opens Na + /K + channel Acetylcholinesterase Synaptic cleft ACh molecules Fusing synaptic vesicle Synaptic vesicle Acetic acid Choline Axon terminal Action potential Axon terminal at neuromuscular junction Sarcolemma of the muscle fiber Nucleus Na + K + Myelinated axon of motor neuron Ca 2+
  • 26. Figure 9.7b : The neuromuscular junction, p. 290. (b) Axon terminal of a motor neuron Junctional folds of the sarcolemma at motor end plate Part of a myofibril Mitochondrion Synaptic cleft T tubule Synaptic vesicle Ca 2+
  • 27. The Neuromuscular Junction
    • The junction between the axonal terminal of a motor neuron and a skeletal muscle fiber separated by a small space called the neuromuscular cleft (synaptic cleft)
    • Each muscle fiber has only one neuromuscular junction
    • The highly folded region of the sarcolemma of the muscle fiber at the neuromuscular junction is called the Motor End Plate – express acetylcholine receptors on the surface
    • A motor neuron and all the muscle fibers it innervates via its axonal terminals is called a motor unit ; motor units come in different sizes – small, medium, large
  • 28. Figure 9.13: A motor unit consists of a motor neuron and all the muscle fibers it innervates , p. 296. (b) (a) Spinal cord Motor neuron cell body Muscle Branching axon to motor unit Muscle fibers Nerve Motor unit 1 Motor unit 2 Muscle fibers Motor neuron axon Axon terminals at neuromuscular junctions
  • 29. Sequence of events in Excitation-Contraction Coupling
    • Motor neuron is activated
    • Axon of motor neuron generates and transmits action potential to the axonal terminals
    • Results in the release of the neurotransmitter, ACETYLCHOLINE from vesicles in the axonal terminals into the neuromuscular cleft
    • Acetylcholine binds to acetylcholine receptors on the motor end plate to cause depolarization which leads to the generation of action potential at the motor end plate
    • The action potential spreads across the entire sarcolemma and into the T-tubules of the triads
    • Results in the release of calcium ions from the terminal cisternae of the triads into the sarcoplasm
    • Calcium ions bind to TnC which results in a conformational change and the removal of tropomyosin from blocking the myosin-binding sites on actin
  • 30. Figure 9.10: Excitation-contraction coupling, p. 292. ADP P i Net entry of Na + initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft Synaptic vesicle Axon terminal ACh ACh ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca 2+ release from terminal cisternae of SR into cytosol. Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process. Removal of Ca 2+ by active transport into the SR after the action potential ends. SR Tropomyosin blockage restored, blocking myosin binding sites onactin; contraction ends and muscle fiber relaxes. Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ 1 2 6 5 4 3
  • 31. Sequence of events –continued
    • With the tropomyosin blockade ended, activated myosin heads = cross bridges bind to the accessible myosin-binding sites on actin
    • Myosin heads are activated when the myosin heads are attached by ADP +Pi (resulting from ATPase hydrolysis of ATP into ADP + Pi)
    • When the ADP and Pi dissociate from the cross bridges, the attached cross bridges change their orientation termed the POWERSTROKE from a right angle to a bent position pulling the attached thin filament inward into the H zone toward the M line = sliding of thin filaments which results on skeletal muscle contraction
    • Cross bridge detachment - NEW ATP molecules bind to the attach myosin heads to cause them to detach .
    • Lack of new ATP results in skeletal muscle contracture termed RIGOR MORTIS - occurs when an individual dies and ATP synthesis ceases - actin and myosin are irreversibly cross linked and skeletal muscles remain contracted
    • Muscle fatigue is a physiological inability of a stimulated skeletal muscle to contract due to ATP DEFICIT – rate of ATP production lags behind ATP demand.
  • 32. Figure 9.12: The cross bridge cycle, p. 295. ATP ADP ADP ATP hydrolysis ADP ATP P i P i Myosin head (high-energy configuration) Myosin head attaches to the actin myofilament, forming a cross bridge. Thin filament As ATP is split into ADP and P i , the myosin head is energized (cocked into the high-energy conformation). Inorganic phosphate (P i ) generated in theprevious contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. Myosin head (low-energy configuration) Thick filament A s new ATP attaches to the myosin head, the link between Myosin and actin weakens, and the cross bridge detaches. 1 2 3 4
  • 33. Factors that affect the strength/force of skeletal muscle contraction
    • Size of motor units activated – larger motor units generate more force than smaller motor units
    • Number of motor units activated – force increases as the number of motor units activated increases
    • Recruitment = smaller motor units are activated first followed by larger motor units
    • Frequency of skeletal muscle activation – force increases as the rate of stimulation by motor neurons increases
    • The length of the sarcomeres prior to contraction – sarcomeres at the optimum length generate the maximum force; sarcomere length below the optimum length ( shortened sarcomeres) results in decreased force; sarcomere length greater than the optimum length ( stretched sarcomeres) results in decreased force of contraction
  • 34. Figure 9.21: Factors influencing force, velocity, and duration of skeletal muscle contraction, p. 304. (a) (b) (c) Increased contractile force Large number of muscle fibers activated Large muscle fibers Asynchronous tetanic contractions Muscle and sarcomere length slightly over 100% of resting length Predominance of fast glycolytic (fatigable) fibers Predominance of slow oxidative (fatigue-resistant) fibers Small load Increased contractile velocity Increased contractile duration
  • 35. Length-Tension Relationship
  • 36. 2 Main Categories of Skeletal Muscle Contraction
    • Isometric Contraction :
    • force(tension) generated by the muscle is increasing at a constant muscle length ( “isometric” = same length); occurs when the weight exceeds the force generated by the muscle
    • Isotonic Contraction :
    • muscle shortens at a relatively constant force
    • ( isotonic = same force); force generated by skeletal muscle exceeds the weight so the skeletal muscle contracts and work is done, such as lifting the weight.
  • 37. Figure 9.20 : Methods of regenerating ATP during muscle activity , p. 303. Creatine Energy source: CP Oxygen use: None Products: 1 ATP per CP, creatine Duration of energy provision: 15s (a) Direct phosphorylation [coupled reaction of creatine phosphate (CP) and ADP] (b) Anaerobic mechanism (glycolysis and lactic acid formation) (c) Aerobic mechanism (aerobic cellular respiration) Energy source: glucose Oxygen use: None Products: 2 ATP per glucose, lactic acid Duration of energy provision: 30–60 s. Energy source: glucose; pyruvic acid; free fatty acids from adipose tissue; amino acids from protein catabolism Oxygen use: Required Products: 38 ATP per glucose, CO 2 , H 2 O Duration of energy provision: Hours O 2 O 2 ATP ATP net gain Glucose (from glycogen breakdown or delivered from blood) Pyruvic acid Glycolysis in cytosol Glucose (from glycogen breakdown or delivered from blood) Pyruvic acid 2 ATP net gain per glucose 38 Lactic acid Released to blood O 2 H 2 O O 2 Fatty acids Amino acids CP ADP Aerobic respiration in mitochondria CO 2
  • 38. Sources of ATP to support skeletal muscle contraction
    • Stored ATP – used first
    • Creatine Phosphate (CP) – ATP produced from direct phosporylation of ADP by CP using the enzyme Creatine Phosphatase:
    • CP + ADP------------  ATP + creatine
    • Aerobic catabolism of glucose – produces the most ATP
    • Anaerobic catabolism of glucose – pyruvic acid is converted into LACTIC ACID which reduces blood pH and contributes to muscle fatigue
    • How is the ATP generated used in skeletal muscle Contraction
    • 1. ATP is hydrolyzed by ATPase to produce ADP and Pi to activate the myosin heads
    • 2. ATP is required for crossbridge detachment
    • 3. ATP is required for the sequestration of calcium ions back into the SR for storage
    • (active transport)
  • 39. 3 Skeletal Muscle Fiber Types
    • 3 major types of skeletal Muscle Fiber types based on:
    • Speed of Contraction – 2 types:
    • slow fibers and fast fibers due to the speed at which Myosin ATPase hydrolyzes ATP
    • Major Pathway for ATP production - 2 ways:
    • aerobic respiration = oxidative fibers types
    • anaerobic respiration using more glycogen = Glycolytic fiber types.
    • Based on the above criteria there are 3 major skeletal muscle types:
    • i) Slow Oxidative Fibers
    • ii) Fast Oxidative Fibers
    • iii) Fast Glycolytic fibers
  • 40. Structural and Functional Characteristics of the 3 Types of Skeletal Muscle Fibers
    • Slow Oxidative Fast Oxidative Fast Glycolytic
    • Characteristics
    • Speed of contraction can figure all this out based on the name of the process
    • Activity of Myosin ATPase again, same as above
    • Pathway for ATP synthesis oxidative = aerobic glycolytic = anaerobic
    • Myoglobin content NEED OXYGEN SO oxidative = high glycolytic = low
    • Color red red-pink white
    • Number of Mitochondria need more in oxidative so oxidative = high and low in glycolytic
    • Number of Capillaries how do you get O2 for ATP? CAPILLARIES…. So oxidative = many instead of few
    • Fiber Diameter smaller fibers diffuse O2 better, so low, intermediate, LARGE
    • Recruitment order (small to large) 1 st 2 nd 3 rd
    • Glycogen content low low high
    • Rate of fatigue slow intermediate high because of lactic acid production
    • Activities suited for endurance intermediate activities (sprinting) burst of energy activity
    • Rate of fatigue
  • 41. Effect of Exercise on Skeletal Muscles
    • Active muscles may increase in size or strength based on which of the 2 major types of exercise used:
    • Aerobic or endurance exercise ( jogging,biking,swimming) changes in the skeletal muscles:
    • increase in capillaries
    • increase in mitochondria
    • increase in myoglobin content
    • Overall, endurance improved = increase in stamina
    • Resistance exercise ( weight lifting, isometric exercises where muscle are pitted against immovable objects)
    • changes in the skeletal muscles:
    • Increase in the size of skeletal muscles = hypertrophy of skeletal muscles occur due to increase in the number of myofibril within each muscle fiber
    • Increase in glycogen content
    • Overall, bulky muscles generate more force = increase in muscle strength
  • 42. Figure 9.25: Innervation of smooth muscle , p. 311. Smooth muscle cell Mucosa Varicosities Autonomic nerve fiber Varicosity Synaptic vesicles Mitochondrion Submucosa Serosa Muscularis externa
  • 43. Smooth Muscle
    • Smooth muscle, the organ, consists of smooth muscle tissue surrounded by endomysium, infiltrated with blood vessels and autonomic nerve fibers.
    • Most smooth muscles form sheets in the walls of hollow organs in the tracts of the body.
    • Smooth muscles contract to move substances down the body’s tracts
    • Structural differences between Smooth muscle and Skeletal muscle
    • i) Smooth muscle lacks striations because the thick filaments and thin filaments are not arranged in alternating pattern but rather, diagonally
    • ii) Smooth muscle lacks sarcomeres
    • iii) Thin filaments in smooth muscle lack troponin; calcium binds to a regulatory protein called CALMODULIN
    • iv) Smooth muscle cells lack Z lines
    • v) Smooth muscle cells contain DENSE BODIES that anchor the thin filaments
    • vi) Smooth muscle cells contain INTERMEDIATE FILAMENTS that resist tension
    • vii) Sarcolemma of smooth muscle cells lack T-tubules rather, the sarcolemma has shallow cavities called CAVEOLAE (caveoli) that contain extracellular fluid rich in calcium
  • 44. Excitation-Contraction Coupling in Smooth Muscle
    • Smooth muscle can be excited to contract by :
          • Pacemaker cells are intrinsic to the smooth muscle; they spontaneously depolarize generating action potentials to stimulate smooth muscle contraction
          • Chemicals such as hormones stimulate smooth muscle to contract or relax
          • Autonomic nerve fibers; the bulbous swellings of the autonomic fibers called VARICOSITIES form junctions with smooth muscle called DIFFUSE JUNCTIONS. When the autonomic nerve fibers are activated , the neurotransmitter released may stimulate the smooth muscle to contract or to relax
  • 45. Figure 9.27: Sequence of events in excitation-contraction coupling of smooth muscle, p. 313. ATP P i P i P i P i ADP Calcium ions (Ca 2+ ) enter the cytosol from the ECF or from the scant SR. Ca 2+ binds to and activates calmodulin. Ca 2+ Ca 2+ Ca 2+ Sarcoplasmic reticulum Plasma membrane Activated calmodulin activates the myosin light chain kinase enzymes. Inactive calmodulin Activated calmodulin Inactive kinase Activated kinase Extracellular fluid Cytoplasm The activated kinase enzyme catalyzes transfer of phosphate to myosin heads, activating the myosin head ATPases. Phosphorylated myosin heads form cross bridges with actin of the thin filaments and shortening occurs. Inactive myosin molecule Activated (phosphorylated) myosin molecule Thin myofilament Thick filament Cross bridge activity ends when phosphate is removed from the myosin heads by phosphorylase enzymes and intracellular Ca 2+ levels fall. 1 2 3 4 5 6
  • 46. Sequence of events in the mechanism of Smooth Muscle Contraction
    • Pacemaker activity, a chemical or autonomic nerve fiber activation leads to increase in intracellular calcium – calcium ions enter the smooth muscle cells from the extracellular fluid in the caveolae and also by release from poorly-developed sarcoplasmic reticulum
    • Calcium binds to Calmodulin
    • Calcium-Calmodulin complex activates myosin light chain kinase( MLCK )
    • Activated MLCK phosphorylates/activates the myosin heads to form cross bridges - attach to the always accessible myosin binding sites on actin (although tropomyosin is present in thin filaments, it does not block myosin binding sites on actin)
    • Upon attachment of cross bridges, sliding of thin filaments occurs = shortening of smooth muscle cells = smooth muscle contraction
    • Cross bridge detachment occurs when the enzyme, phosphorylase , removes the phosphate from the myosin heads
  • 47. 2 Types of Smooth Muscle
    • Based on smooth muscle fiber arrangement, innervation and responsiveness to stimuli
    • i) Single-Unit Smooth Muscle:
      • Composed of circular and longitudinal smooth muscle sheets
      • Innervated by autonomic nerve fibers
      • Electrically-coupled by gap junctions hence, single-unit smooth muscle contracts as a unit
      • Stimulated to contract by chemicals
      • Exhibit pacemaker activity
    • ii) Multiunit Smooth Muscle:
      • Composed of individual smooth muscle fibers
      • Lacks gap junctions – smooth muscle cells contract independently of each other
      • Innervated by the autonomic nerve fibers
      • Stimulated to contract by chemicals
      • No pacemaker activity