Muscular System: Histology and Physiology

1. Chapter 9 Muscular System:Histology and Physiology

2. Functions of the Muscular System • Body movement (skeletal muscles attached to bones) • Maintenance of posture • Respiration (skeletal muscles of thorax are responsible for the movement necessary for respiration) • Production of body heat (when skeletal muscles contact, heat is given off as a by-product) • Communication (speaking, writing) • Constriction of organs and vessels (contraction of smooth muscle) • Heart beat (contraction of cardiac muscle)

3. General Functional Characteristics of Muscle • Contractility: ability of a muscle to shorten with force • Excitability: capacity of muscle to respond to a stimulus (by nerve or hormone) • Extensibility: muscle can be stretched to its normal resting length and beyond to a limited degree • Elasticity: ability of muscle to recoil to original resting length after stretched

4. Types of Muscle Tissue • Skeletal • Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement • Voluntary • Smooth • Walls of hollow organs, blood vessels, eye, glands, skin • Some functions: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow • In some locations, autorhythmic • Controlled involuntarily by endocrine and autonomic nervous systems • Cardiac • Heart: major source of movement of blood • Autorhythmic • Controlled involuntarily by endocrine and autonomic nervous systems

6. Skeletal Muscle Structure • Composed of muscle cells (fibers), connective tissue, blood vessels, nerves • Fibers are long, cylindrical, multinucleated • Tend to be smaller diameter in small muscles and larger in large muscles. 1 mm- 4 cm in length • Develop from myoblasts (they are converted to muscle fibers as contractile proteins accumulate within their cytoplasm); numbers remain constant (# of muscle fibers remain constant after birth----so, enlargement of muscles is an increase in size rather than #) • Striated appearance due to light and dark banding

7. Connective Tissue Coverings of Muscle • Layers • External lamina. Delicate, reticular fibers. Surrounds sarcolemma (P.M.) • Endomysium. Loose C.T. with reticular fibers. • Perimysium. Denser C.T. surrounding a group of muscle fibers. Each group called a fasciculus • Epimysium. C.T. that surrounds a whole muscle (many fascicles) • Fascia: connective tissue sheet • Forms layer under the skin • Holds muscles together and separates them into functional groups. • Allows free movements of muscles. • Carries nerves (motor neurons, sensory neurons), blood vessels, and lymphatics. • Continuous with connective tissue of tendons and periosteum.

8. Nerves and Blood Vessel Supply • Motor neurons: stimulate muscle fibers to contract. Nerve cells with cell bodies in brain or spinal cord; axons extend to skeletal muscle fibers through nerves • Axons branch so that each muscle fiber is innervated • Capillary beds surround muscle fibers

9. Muscle Fibers • Nuclei just inside sarcolemma • Cell packed with myofibrils within cytoplasm (sarcoplasm = cytoplasm without myofibrils) • Threadlike (extends from one end of muscle fiber to the other) • Composed of protein threads called myofilaments: thin (actin 8nm) and thick (myosin 12nm) • Sarcomeres: actin & myosin myofilaments form highly ordered units called sarcomeres. They are joined end to end to form the myofibrils.

10. Parts of a Muscle

11. Actin and Myosin Myofilaments

12. Actin (Thin) Myofilaments • Two strands of fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere. • Composed of G actin monomers each of which has an active site • Actin site can bind myosin during muscle contraction. • Tropomyosin: an elongated protein winds along the groove of the F actin double helix. • Troponin is composed of three subunits: one that binds to actin, a second that binds to tropomyosin, and a third that binds to calcium ions. Spaced between the ends of the tropomyosin molecules in the groove between the F actin strands. • The tropomyosin/troponin complex regulates the interaction between active sites on G actin and myosin.

13. Myosin (Thick) Myofilament • Many elongated myosin molecules shaped like golf clubs. • Molecule consists of two heavy myosin molecules wound together to form a rod portion lying parallel to the myosin myofilament and two heads that extend laterally. • Myosin heads • Can bind to active sites on the actin molecules to form cross-bridges. • Attached to the rod portion by a hinge region that can bend and straighten during contraction. • Have ATPase activity: activity that breaks down adenosine triphosphate (ATP), releasing energy. Part of the energy is used to bend the hinge region of the myosin molecule during contraction

14. Sarcomeres: Z Disk to Z Disk • Z disk: filamentous network of protein. Serves as attachment for actin myofilaments • Striated appearance • I bands: from Z disks to ends of thick filaments • A bands: length of thick filaments • H zone: region in A band where actin and myosin do not overlap • M line: middle of H zone; delicate filaments holding myosin in place • In muscle fibers, A and I bands of parallel myofibrils are aligned. • Titin filaments: elastic chains of amino acids; make muscles extensible and elastic

15. Sliding Filament Model • Actin myofilaments slidingover myosin to shorten sarcomeres • Actin and myosin do not change length • Shortening sarcomeres responsible for skeletal muscle contraction • During relaxation, sarcomeres lengthen because of some external force, like forces produced by other muscles (contraction of antagonistic muscles)or by gravity. - agonist = muscle that accomplishes a certain movement, such as flexion. - antagonist = muscle acting in opposition to agonist.

16. Sarcomere Shortening

17. Physiology of Skeletal Muscle Fibers • Nervous system controls muscle contractions through action potentials • Resting membrane potentials • Membrane voltage difference across membranes (polarized) • Inside cell more negative due to accumulation of large protein molecules. More K+ on inside than outside. K+ leaks out (through leak channels) but not completely because negative molecules hold some back. • Outside cell more positive and more Na+ on outside than inside. • Na+ /K+ pump maintains this situation. • Must exist for action potential to occur

18. Ion Channels • Types • Ligand-gated. Ligands are molecules that bind to receptors. Receptor: protein or glycoprotein with a receptor site • Example: neurotransmitters • Gate is closed until neurotransmitter attaches to receptor molecule. When Ach (acetylcholine) attaches to receptor on muscle cell, Na gate opens. Na moves into cell due to concentration gradient • Voltage-gated • Open and close in response to small voltage changes across plasma membrane • Each is specific for one type of ion

19. Action Potentials • Phases • Depolarization: Inside of plasma membrane becomes less negative. If change reaches threshold, depolarization occurs • Repolarization: return of resting membrane potential. Note that during repolarization, the membrane potential drops lower than its original resting potential, then rebounds. This is because Na plus K together are higher, but then Na/K pump restores the resting potential • All-or-none principle: like camera flash system • Propagate: Spread from one location to another. Action potential does not move along the membrane: new action potential at each successive location. • Frequency: number of action potential produced per unit of time

20. Gated Ion Channels and the Action Potential

21. Action Potential Propagation

22. Neuromuscular Junction • Synapse: axon terminal resting in an invagination of the sarcolemma • Neuromuscular junction (NMJ): • Presynaptic terminal: axon terminal with synaptic vesicles • Synaptic cleft: space • Postsynaptic membrane or motor end-plate

23. Function of Neuromuscular Junction • Synaptic vesicles • Neurotransmitter: substance released from a presynaptic membrane that diffuses across the synaptic cleft and stimulates (or inhibits) the production of an action potential in the postsynaptic membrane. • Acetylcholine • Acetylcholinesterase: A degrading enzyme in synaptic cleft. Prevents accumulation of ACh

25. Excitation-Contraction Coupling • Mechanism by which an action potential causes muscle fiber contraction • Involves • Sarcolemma • Transverse (T) tubules: invaginations of sarcolemma • Terminal cisternae • Sarcoplasmic reticulum: smooth ER • Triad: T tubule, two adjacent terminal cisternae • Ca2+ • Troponin

26. Action Potentials and Muscle Contraction

27. Cross-Bridge Movement

28. Relaxation • Ca2+ moves back into sarcoplasmic reticulum by active transport. Requires energy • Ca2+ moves away from troponin-tropomyosin complex • Complex re-establishes its position and blocks binding sites.

29. Muscle Twitch • Muscle contraction in response to a stimulus that causes action potential in one or more muscle fibers • Muscle contraction measures as force, also called tension. Requires up to a second to occur. • Phases • Lag or latent (neuromuscular junction & step #1 of cross-bridge movement) • Contraction (step #2 - #6 of cross-bridge movement) • Relaxation (powerpoint slide # 28)

31. Stimulus Strength and Muscle Contraction • All-or-none law for muscle fibers • Contraction of equal force in response to each action potential • Sub-threshold stimulus: no action potential; no contraction • Threshold stimulus: action potential; contraction • Stronger than threshold; action potential; contraction equal to that with threshold stimulus • Motor units: a single motor neuron and all muscle fibers innervated by it

32. Contraction of the Whole Muscle • Whole muscles exhibit characteristics that are more complex than those of individual muscle fibers or motor units. Instead of responding in an all-or-none fashion, whole muscles respond to stimuli in a graded fashion, which means that the strength of the contractions can range from weak to strong. • Remember: There are many muscle fibers in one fasciculi and many fasciculi in one whole muscle. • Strength of contraction in whole muscle is graded: ranges from weak to strong depending on stimulus strength • Multiple motor unit summation: the force in which a whole muscle contracts depends on the number of motor units stimulated to contract. (force of contraction increases as more & more motor units are stimulated). A muscle has many motor units • Submaximal stimuli • Maximal stimulus • Supramaximal stimuli

33. Contraction of the Whole Muscle

34. Stimulus Frequency and Muscle Contraction • Relaxation of a muscle fiber is not required before a second action potential can stimulate a second contraction. • As the frequency of action potentials increase, the frequency of contraction increases • Incomplete tetanus:muscle fibers partially relax between contraction • Complete tetanus:no relaxation between contractions • Multiple-wave summation:muscle tension increases as contraction frequencies increase

35. Types of Muscle Contractions • Isometric: no change in length of muscle but tension increases during contraction • Postural muscles of body ex: muscles hold spine erect while person is sitting or standing • Isotonic: change in length but tension constant ex: waving using computer keyboard • Concentric: tension is so great it overcomes opposing resistance and muscle shortens ex: raising of a weight during a bicep curl. • Eccentric: tension maintained but muscle lengthens ex: person slowly lowers a heavy weight • Muscle tone: constant tension by muscles for long periods of time

36. Fatigue • Decreased capacity to work and reduced efficiency of performance • Types • Psychological: depends on emotional state of individual ex: burst of activity in tired athlete in response to encouragement from spectators shows how psychological fatigue can be overcome • Muscular: results from ATP depletion ex: fatigue in lower limbs of marathon runners or in upper & lower limbs of swimmers • Synaptic: occurs in NMJ due to lack of acetylcholine ex: rare-----only under extreme exertion

37. Physiological Contracture and Rigor Mortis • Physiological contracture: state of extreme fatigue (extreme exercise) where due to lack of ATP neither contraction nor relaxation can occur • Rigor mortis: development of rigid muscles several hours after death. Ca2+ leaks into sarcoplasm and attaches to myosin heads and crossbridges form but no ATP available to bind to myosin---------so the cross-bridges are unable to release. Rigor ends as tissues start to deteriorate.

38. Energy Sources • ATP provides immediate energy for muscle contractions. Produced from three sources • Creatine phosphate • During resting conditions stores energy to synthesize ATP • ADP + Creatine phosphate------------------ Creatine + 1ATP (Creatine Kinase) • Anaerobic respiration • Occurs in absence of oxygen and results in breakdown of glucose to yield ATP and lactic acid • Aerobic respiration • Requires oxygen and breaks down glucose to produce ATP, carbon dioxide and water • More efficient than anaerobic

39. Slow and Fast Fibers • Slow-twitchoxidative • Contract more slowly, smaller in diameter, better blood supply, more mitochondria (also called oxidative because carry out aerobic respiration), more fatigue-resistant than fast-twitch, large amount of myoglobin (dark pigment which binds oxygen & acts as a muscle reservoir for oxygen when blood does not supply adequate amount). • Postural muscles, more in lower than upper limbs. Dark meat of chicken. • Functions: Maintenance of posture & performance in endurance activities. • Fast-twitch • Respond rapidly to nervous stimulation, contain myosin that can break down ATP more rapidly than that in Type I, less blood supply, fewer and smaller mitochondria than slow-twitch (adapted to perform anaerobic respiration) • Lower limbs in sprinter, upper limbs of most people. White meat in chicken. • Comes in oxidative and glycolytic forms • Functions: Rapid, intense movements of short duration • Distribution of fast-twitch and slow-twitch • Most muscles have both but varies for each muscle • Exercise: weight lifting enlarges fast-twitch & aerobic training enlarges slow-twitch • Effects of exercise: change in size of muscle fibers • Hypertrophy: increase in muscle size • Increase in myofibrils • Increase in nuclei due to fusion of satellite cells • Increase in strength • Atrophy: decrease in muscle size • Reverse except in severe situations where cells die

41. Smooth Muscle • Not striated, fibers smaller than those in skeletal muscle • Spindle-shaped; single, central nucleus • More actin than myosin • Caveolae: indentations in sarcolemma; may act like T tubules • Dense bodies instead of Z disks as in skeletal muscle; have noncontractile intermediate filaments • Ca2+ required to initiate contractions; binds to calmodulin (protein). Calmodulin molecules with Ca++ bound to them activate an enzyme called myosin kinase, which transfers a phosphate group from ATP to heads of myosin molecules. Cross-bridging occurs • Relaxation: caused by enzyme myosin phosphatase

43. Electrical Properties of Smooth Muscle • Slow waves of depolarization and repolarization transferred from cell to cell • Depolarization caused by spontaneous diffusion of Na+ and Ca2+ into cell • Does not follow all-or-none law • Contraction regulated by nervous system and by hormones (ex: epinephrine)

44. Regulation of Smooth Muscle • Innervated by autonomic nervous system(composed of nerve fibers that send impulses from CNS to smooth muscle, cardiac muscle, glands) • Neurotransmitters are acetylcholine and norepinephrine (increases cardiac output, blood glucose levels) • Hormones important as epinephrine and oxytocin • Receptors present on plasma membrane; which neurotransmitters or hormones bind determines response

45. Cardiac Muscle • Found only in heart • Striated • Each cell usually has one nucleus • Has intercalated disks and gap junctions • Autorhythmic cells • Action potentials of longer duration • The depolarization of cardiac muscle results from influx of Na+ and Ca2+ across the plasma membrane

46. Effects of Aging on Skeletal Muscle • Reduced muscle mass • Increased time for muscle to contract in response to nervous stimuli • Reduced stamina • Increased recovery time • Loss of muscle fibers