Introduction to Muscle

1. Movement is a fundamental characteristic of all living things • Cells capable of shortening and converting the chemical energy of ATP into mechanical energy • Types of muscle • skeletal, cardiac and smooth • Physiology of skeletal muscle • basis of warm-up, strength, endurance and fatigue Introduction to Muscle

2. Movement of body parts and organ contents Maintain posture and prevent movement Communication - speech, expression and writing Control of openings and passageways Heat production The Functions of Muscles

3. Responsiveness (excitability) • to chemical signals, stretch and electrical changes across the plasma membrane • Conductivity • local electrical change triggers a wave of excitation that travels along the muscle fiber • Contractility -- shortens when stimulated • Extensibility -- capable of being stretched • Elasticity -- returns to its original resting length after being stretched Characteristics of Muscle

4. Each muscle is composed of muscle tissue, blood vessels, nerve fibers, and connective tissue • The three connective tissue sheaths are: • Endomysium – fine sheath of connective tissue composed of reticular fibers surrounding each muscle fiber • Endomysium surrounds muscle fiber • Perimysium – fibrous connective tissue that surrounds groups of muscle fibers called fascicles • Perimysium surrounds fascicles of muscle fibers • Epimysium – an overcoat of dense regular connective tissue that surrounds the entire muscle • Epimysium surrounds entire muscle Skeletal muscle Tendon Deep fascia Epimysium Perimysium Endomysium

5. Direct (fleshy) attachment to bone • epimysium is continuous with periosteum • intercostal muscles • Indirect attachment to bone • epimysium continues as tendon or aponeurosis that merges into periosteum as perforating fibers • biceps brachii or abdominal muscle • Attachment to dermis • Stress will tear the tendon before pulling the tendon loose from either muscle or bone Muscle Attachments

6. Voluntary striated muscle with multiple nuclei • Muscle fibers (myofibers) as long as 30 cm • Exhibits alternating light and dark transverse bands or striations • reflects overlapping arrangement of internal contractile proteins • Under conscious control (voluntary) Skeletal Muscle

7. Muscle Fibers • Multiple flattened nuclei inside cell membrane • fusion of multiple myoblasts during development • unfused satellite cells nearby can multiply to produce a small number of new myofibers • Sarcolemma has tunnel-like infoldings or transverse (T) tubules that penetrate the cell • carry electric current to cell interior form triad with sacoplasmic reticulum (SR)

8. Muscle Fibers 2 • Sarcoplasm is filled with • myofibrils (bundles of myofilaments) • glycogen for stored energy and myoglobin for binding oxygen • Sarcoplasmic reticulum = smooth ER • network around each myofibril • dilated end-sacs (terminal cisternea) store calcium • triad = T tubule and 2 terminal cisternae

9. Made of 200 to 500 myosin molecules • 2 entwined polypeptides (golf clubs) • Arranged in a bundle with heads directed outward in a spiral array around the bundled tails • central area is a bare zone with no heads Thick Filaments

10. Two intertwined strands fibrous (F) actin • globular (G) actin with an active site • Groove holds tropomyosin molecules • each blocking 6 or 7 active sites of G actins • One small, calcium-binding troponin molecule on each tropomyosin molecule Thin Filaments

11. Elastic Filaments • Springy proteins called titin • Anchor each thick filament to Z disc • Prevents overstretching of sarcomere

12. Dark A bands (regions) alternating with lighter I bands (regions) • A band is thick filament region • lighter, central H band area contains no thin filaments • I band is thin filament region • bisected by Z disc protein called connectin, anchoring elastic and thin filaments • from one Z disc (Z line) to the next is a sarcomere Striations = Organization of Filaments

13. Striations and Sarcomeres

14. Overlap of Thick and Thin Filaments

15. Myosin and actin are contractile proteins • Tropomyosin and troponin = regulatory proteins • switch that starts and stops shortening of muscle cell • contraction activated by release of calcium into sarcoplasm and its binding to troponin, • troponin moves tropomyosin off the actin active sites Contractile and Regulatory Proteins

16. Muscle cells shorten because their individual sarcomeres shorten • pulling Z discs closer together • pulls on sarcolemma • Notice neither thick nor thin filaments change length during shortening • Their overlap changes as sarcomeres shorten Relaxed and Contracted Sarcomeres Animation

17. Functional connection between nerve fiber and muscle cell • Neurotransmitter (acetylcholine/ACh) released from nerve fiber stimulates muscle cell • Components of synapse (NMJ) • synaptic knob is swollen end of nerve fiber (contains ACh) • junctional folds region of sarcolemma with ACh receptors • synaptic cleft = tiny gap between nerve and muscle cells • basal lamina = thin layer of collagen and glycoprotein over all of muscle fiber Neuromuscular Junctions (Synapse)

18. Plasma membrane is polarized or charged • resting membrane potential due to Na+ outside of cell and K+ and other anions inside of cell • difference in charge across the membrane = resting membrane potential (-90 mV) • Stimulation opens ion gates in membrane • ion gates open (Na+ rushes into cell and K+ rushes out of cell) • quick up-and-down voltage shift = action potential • spreads over cell surface (both in muscle and nerve cells) Electrically Excitable Cells

19. Four actions involved in this process • excitation = nerve action potentials lead to action potentials in muscle fiber • excitation-contraction coupling = action potentials on the sarcolemma activate myofilaments • contraction = shortening of muscle fiber • relaxation = return to resting length • Images will be used to demonstrate the steps of each of these actions Muscle Contraction and Relaxation

20. Nerve signal opens voltage-gated calcium channels. Calcium stimulates exocytosis of synaptic vesicles containing ACh = ACh release into synaptic cleft. Excitation (steps 1 and 2)

21. Excitation (steps 3 and 4) Binding of ACh to receptor proteins opens Na+ and K+ channels resulting in jump in RMP from -90mV to +75mV forming an end-plate potential (EPP).

22. Excitation (step 5) Voltage change in end-plate region (EPP) opens nearby voltage-gated channels producing an action potential

23. Action potential spreading over sarcolemma enters T tubules -- voltage-gated channels open in T tubules causing calcium gates to open in SR Excitation-Contraction Coupling (steps 6 and 7)

24. Excitation-Contraction Coupling (steps 8 and 9) • Calcium released by SR binds to troponin • Troponin-tropomyosin complex changes shape and exposes active sites on actin

25. Myosin ATPase in myosin head hydrolyzes an ATP molecule, activating the head and “cocking” it in an extended position It binds to actin active site forming a cross-bridge Contraction (steps 10 and 11)

26. Power stroke = myosin head releases ADP and phosphate as it flexes pulling the thin filament past the thick • With the binding of more ATP, the myosin head extends to attach to a new active site • half of the heads are bound to a thin filament at one time preventing slippage • thin and thick filaments do not become shorter, just slide past each other (sliding filament theory) Contraction (steps 12 and 13) Animation

27. Nerve stimulation ceases and acetylcholinesterase removes ACh from receptors. Stimulation of the muscle cell ceases. Relaxation (steps 14 and 15)

28. Active transport needed to pump calcium back into SR to bind to calsequestrin ATP is needed for muscle relaxation as well as muscle contraction Relaxation (step 16)

29. Loss of calcium from sarcoplasm moves troponin-tropomyosin complex over active sites • stops the production or maintenance of tension • Muscle fiber returns to its resting length due to recoil of series-elastic components and contraction of antagonistic muscles Relaxation (steps 17 and 18)

30. Stiffening of the body beginning 3 to 4 hours after death Deteriorating sarcoplasmic reticulum releases calcium Calcium activates myosin-actin cross-bridging and muscle contracts, but can not relax. Muscle relaxation requires ATP and ATP production is no longer produced after death Fibers remain contracted until myofilaments decay Rigor Mortis

31. Pesticides (cholinesterase inhibitors) • bind to acetylcholinesterase and prevent it from degrading ACh • spastic paralysis and possible suffocation • Flaccid paralysis (limp muscles) due to curare that competes with ACh • respiratory arrest Neuromuscular Toxins

32. Skeletal muscle must be stimulated by a nerve or it will not contract • Axons of somatic motor neurons = somatic motor fibers • terminal branches supply one muscle fiber • Each motor neuron and all the muscle fibers it innervates = motor unit Nerve-Muscle Relationships

33. A motor neuron and the muscle fibers it innervates • dispersed throughout the muscle • when contract together causes weak contraction over wide area • provides ability to sustain long-term contraction as motor units take turns resting (postural control) • Fine control • small motor units contain as few as 20 muscle fibers per nerve fiber • eye muscles • Strength control • gastrocnemius muscle has 1000 fibers per nerve fiber Motor Units

34. Amount of tension generated depends on length of muscle before it was stimulated • length-tension relationship • Overly contracted (weak contraction results) • thick filaments too close to Z discs and can’t slide • Too stretched (weak contraction results) • little overlap of thin and thick does not allow for very many cross bridges too form • Optimum resting length produces greatest force when muscle contracts • central nervous system maintains optimal length producing muscle tone or partial contraction Length-Tension Relationship

35. Threshold = voltage producing an action potential • a single brief stimulus at that voltage produces a quick cycle of contraction and relaxation called a twitch (lasting less than 1/10 second) • A single twitch contraction is not strong enough to do any useful work Muscle Twitch in Frog

36. Phases of a twitch contraction • latent period (2 msec delay) • only internal tension is generated • no visible contraction occurs – elastic components are being stretched • contraction phase • external tension develops as muscle shortens • relaxation phase • loss of tension and return to resting length as calcium returns to SR Muscle Twitch in Frog 2

37. Threshold stimuli produces twitches • Twitches unchanged despite increased voltage • “Muscle fiber obeys an all-or-none law” contracting to its maximum or not at all • not a true statement since twitches vary in strength • depending upon, Ca2+ concentration, previous stretch of the muscle, temperature, pH and hydration • Closer stimuli produce stronger twitches Contraction Strength of Twitches

38. Recruitment and Stimulus Intensity • Stimulating the whole nerve with higher and higher voltage produces stronger contractions • More motor units are being recruited • called multiple motor unit summation • lift a glass of milk versus a whole gallon of milk

39. Twitch and Treppe Contractions • Muscle stimulation at variable frequencies • low frequency (up to 10 stimuli/sec) • each stimulus produces an identical twitch response • moderate frequency (between 10-20 stimuli/sec) • each twitch has time to recover but develops more tension than the one before (treppe phenomenon) • calcium was not completely put back into SR • heat of tissue increases myosin ATPase efficiency

40. Incomplete and Complete Tetanus • Higher frequency stimulation (20-40 stimuli/second) generates gradually more strength of contraction • each stimuli arrives before last one recovers • temporal summation or wave summation • incomplete tetanus = sustained fluttering contractions • Maximum frequency stimulation (40-50 stimuli/second) • muscle has no time to relax at all • twitches fuse into smooth, prolonged contraction called complete tetanus • rarely occurs in the body

41. Isometric muscle contraction • develops tension without changing length • important in postural muscle function and antagonistic muscle joint stabilization • Isotonic muscle contraction • tension while shortening = concentric • tension while lengthening = eccentric Isometric and Isotonic Contractions

42. All muscle contraction depends on ATP • Pathways of ATP synthesis • anaerobic fermentation (ATP production limited) • without oxygen, produces toxic lactic acid • aerobic respiration (more ATP produced) • requires continuous oxygen supply, produces H2O and CO2 ATP Sources

43. Short, intense exercise (100 m dash) • oxygen need is supplied by myoglobin • Phosphagen system • myokinase transfers Pi groups from one ADP to another forming ATP • creatine kinase transfers Pi groups from creatine phosphate to make ATP • Result is power enough for 1 minute brisk walk or 6 seconds of sprinting Immediate Energy Needs

44. Glycogen-lactic acid system takes over • produces ATP for 30-40 seconds of maximum activity • playing basketball or running around baseball diamonds • muscles obtain glucose from blood and stored glycogen Short-Term Energy Needs

45. Aerobic respiration needed for prolonged exercise • Produces 36 ATPs/glucose molecule • After 40 seconds of exercise, respiratory and cardiovascular systems must deliver enough oxygen for aerobic respiration • oxygen consumption rate increases for first 3-4 minutes and then levels off to a steady state • Limits are set by depletion of glycogen and blood glucose, loss of fluid and electrolytes Long-Term Energy Needs

46. Progressive weakness from use • ATP synthesis declines as glycogen is consumed • sodium-potassium pumps fail to maintain membrane potential and excitability • lactic acid inhibits enzyme function • accumulation of extracellular K+ hyperpolarizes the cell • motor nerve fibers use up their acetylcholine Fatigue

47. Ability to maintain high-intensity exercise for >5 minutes • determined by maximum oxygen uptake • VO2 max is proportional to body size, peaks at age 20, is larger in trained athlete and males • nutrient availability • carbohydrate loading used by some athletes • packs glycogen into muscle cells • adds water at same time (2.7 g water with each gram/glycogen) • side effects include “heaviness” feeling Endurance

48. Heavy breathing after strenuous exercise • known as excess postexercise oxygen consumption (EPOC) • typically about 11 liters extra is consumed • Purposes for extra oxygen • replace oxygen reserves (myoglobin, blood hemoglobin, in air in the lungs and dissolved in plasma) • replenishing the phosphagen system • reconverting lactic acid to glucose in kidneys and liver • serving the elevated metabolic rate that occurs as long as the body temperature remains elevated by exercise Oxygen Debt

49. Slow oxidative, slow-twitch fibers • more mitochondria, myoglobin and capillaries • adapted for aerobic respiration and resistant to fatigue • soleus and postural muscles of the back (100msec/twitch) Slow- and Fast-Twitch Fibers

50. Fast glycolytic, fast-twitch fibers • rich in enzymes for phosphagen and glycogen-lactic acid systems • sarcoplasmic reticulum releases calcium quickly so contractions are quicker (7.5 msec/twitch) • extraocular eye muscles, gastrocnemius and biceps brachii • Proportions genetically determined Slow and Fast-Twitch Fibers