Muscle Fiber Anatomy

1. Muscle Fiber Anatomy Sarcolemma - cell membrane Surrounds the sarcoplasm (cytoplasm of fiber) Contains many of the same organelles seen in other cells An abundance of the oxygen-binding protein myoglobin Punctuated by openings called the transverse tubules (T-tubules) Narrow tubes that extend into the sarcoplasm at right angles to the surface Filled with extracellular fluid Myofibrils -cylindrical structures within muscle fiber Are bundles of protein filaments (=myofilaments) Two types of myofilaments Actin filaments (thin filaments) Myosin filaments (thick filaments) At each end of the fiber, myofibrils are anchored to the inner surface of the sarcolemma When myofibril shortens, muscle shortens (contracts) Myofibrils surrounded by sarcoplasmic Reticulum, a calcium-containing network of tubules

2. Sarcoplasmic Reticulum (SR) SR is an elaborate, smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril Form chambers called terminal cisternae on either side of the T-tubules A single T-tubule and the 2 terminal cisternae form a triad SR has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR

3. Sarcoplasmic Reticulum (SR) SR is an elaborate, smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril Form chambers called terminal cisternae on either side of the T-tubules A single T-tubule and the 2 terminal cisternae form a triad SR has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR

4. Sarcoplasmic Reticulum (SR)

5. Structure of Actin and Myosin

6. 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: Tn-I site: binds to actin Tn-T site: binds to tropomyosin Tn-C site: binds to calcium ions The tropomyosin/troponin complex regulates the interaction between active sites on G actin and myosin.

7. 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

8. Sarcomeres 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

9. Striations and Sarcomeres

10. Nerve-Muscle Relationships Skeletal muscle must be stimulated by a motor neuron or it will not contract Cell bodies of somatic motor neurons in brainstem or spinal cord Anterior horn motor neurons (AHMN) Axons of these AHMN�s form terminal branches with synaptic bulbs Each terminal branch supplies one muscle fiber Each motor neuron and all the muscle fibers it innervates = motor unit

11. White Matter: Pathway Generalizations

12. Descending (Motor) Pathways Descending tracts deliver motor impulses from the brain to the spinal cord Motor pathways involve two neurons Upper motor neuron (UMN) Originates (cell body) in brain Its axons form the projection tracts of the brain Synapses with LMN in spinal cord Lower motor neuron (LMN): AHMN Originates (cell body) in anterior horn Myelinated axon exits cord via ventral root and enters spinal nerve Its synaptic knobs form the neuromuscular junction (aka, myoneural junction)

13. Pyramidal (Corticospinal) Tracts Originate in the precentral gyrus of brain (aka, primary motor area) I.e., cell body of the UMN located in precentral gyrus Pyramidal neuron is the UMN Its axon forms the corticospinal tract UMN synapses in the anterior horn with LMN Some UMN decussate in pyramids = Lateral corticospinal tracts Others decussate at other levels of s.c. = Anterior corticospinal tracts LMN (anterior horn motor neurons) Exits spinal cord via anterior root Activates skeletal muscles Regulates fast and fine (skilled) movements

14. Corticospinal tracts

15. Motor Units Def: A motor neuron and all the muscle fibers it innervates Fibers aredispersed throughout the muscle When contracted together cause a weak contraction over wide area provides ability to sustain long-term contraction as motor units take turns resting (postural control) Fine control of muscles small motor units contain as few as 4-6 muscle fibers per nerve fiber Extraocular muscles (move eyeball) Strength control Gastrocnemius muscle has 1000-1500muscle fibers per nerve fiber

16. Neuromuscular Junctions (Synapse) Functional connection between nerve fiber and muscle cell Neurotransmitter (acetylcholine/ACh) released from nerve fiber stimulates muscle fiber Components of synapse (NMJ) synaptic knob is swollen end of axon terminal contains ACh Motor end plate: region of sarcolemma that abuts the synaptic knob; highly folded increases surface area allowing for more ACh receptors contain acetylcholinesterase that breaks down ACh and causes relaxation synaptic cleft = tiny gap between synaptic knob and sarcolemma of muscle fiber

17. The Neuromuscular Junction

18. Muscle Fibers are Excitable Sarcolemma 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 cell) Stimulation (ACh binding to cholinergic receptors) opens ion gates in sarcolemma 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 as an action potential

19. Muscle Contraction and Relaxation 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

20. Explains the relationship between thick and thin filaments as contraction proceeds Cyclic process beginning with calcium release from SR Calcium binds to troponin Troponin moves, moving tropomyosin and exposing actin active site Myosin head forms cross bridge and bends toward H zone (pulling actin inward) ATP allows release of cross bridge Sliding Filament Theory

21. Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber

22. Created when muscles contract Series of steps that begin with excitation at the neuromuscular junction Calcium release Thick/thin filament interaction Muscle fiber contraction Tension Tension

23. Excitation-Contraction Coupling

24. Sequential Events of Contraction

25. Rigor Mortis 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

27. The Effect of Sarcomere Length on Tension Amount of tension (force) generated by the muscle depends on length of muscle before it was stimulated length-tension relationship (see graph next slide) Overly contracted (weak contraction results)- See Fig. 1 on left side on next slide thick filaments too close to Z discs and can�t slide Too stretched (weak contraction results) Fig. 3 on right side on next slide little overlap of thin and thick filaments does not allow for very many cross bridges too form Optimum resting length (Lo) produces greatest force when muscle contracts Fig. 2 in center central nervous system maintains optimal length producing muscle tone or partial contraction

28. The Effect of Sarcomere Length on Tension Active tension: force applied to an object to be lifted when a muscle contracts Load - the object being acted upon by the muscle Stretched muscle- not enough cross-bridging Crumpled muscle- myofilaments crumpled, cross-bridges can't contract

29. Muscle Twitch A muscle twitch is the response of a muscle fiber to a single, brief threshold stimulus The three phases of a muscle twitch are: Latent period (2 msec delay) No visible contraction occurs; no tension developed Processes of �excitation-contraction coupling� occurring Contraction phase External tension develops as muscle shortens Not all skeletal muscle fibers have same contraction time Fast twitch fibers = 10 msec; Slow twitch fibers = 100 msec Relaxation phase Loss of tension and return to resting length as calcium returns to SR

30. Muscle Twitch 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 = 100 msc) A single twitch contraction is not strong enough to do any useful work

31. The Twitch and the Development of Tension

32. Effects of Repeated Stimulations

33. Twitch and Treppe Contractions Muscle stimulation at variable frequencies low frequency (up to 10 stimuli/sec)- Fig A above 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

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

35. Motor Units Def: A motor neuron and all the muscle fibers it innervates Fibers are dispersed throughout the muscle Provides ability to sustain long-term contraction as motor units take turns resting (postural control) Fine control of muscles small motor units contain as few as 4-6 muscle fibers per nerve fiber Extraocular muscles (move eyeball) Strength control Gastrocnemius muscle has 1200-1500muscle fibers per nerve fiber

36. Stimulus Intensity and Muscle Tension  Muscle contracts more vigorously as stimulus strength is increased Force of contraction precisely controlled by MMUS Multiple Motor Unit Summation or recruitment Recruitment brings more and more motor units into play Note that as the stimulus intensity increases (Fig. 1) more and more motor units are stimulated (Fig.2) and thus the strength of muscle contraction increases (Fig. 3).

37. The Arrangement of Motor Units in a Skeletal Muscle

38. Force of Muscle Contraction The force of contraction is affected by: The relative size of the muscle Larger muscles have larger and more muscle fibers Larger fibers can generate more force than smaller fibers More muscle fibers can generate more force than fewer fibers The number of muscle fibers contracting Greater numbers of motor units generate more force than smaller numbers of motor units Degree of muscle stretch Muscles contract strongest when muscle fibers are 80-120% of their normal resting length

39. Force of Muscle Contraction

40. Isometric and Isotonic Contractions Isometric muscle contraction Tension (force) does not exceed resistance (load) important in postural muscle function Isotonic muscle contraction Tension exceeds resistance tension while shortening = concentric tension while lengthening = eccentric

41. Muscle contraction requires large amounts of energy ATP provides immediate energy for muscle contrac- tions. Produced from three sources Creatine phosphate (CP) Most rapid method of ATP generation Only 1 ATP per CP used Aerobic respiration Requires oxygen and breaks down glucose to produce ATP, carbon dioxide and water Most efficient method Generates 36 ATP per glucose molecule Anaerobic respiration (Glycolysis) Occurs in absence of oxygen Results in breakdown of glucose to yield ATP and lactic acid

42. Muscle Metabolism: Energy for Contraction

43. Short-Term Energy Needs Creatine phosphate system ADP + CP creatine kinase C + ATP CP levels quickly exhausted during intense contractions Able to sustain maximum contractions for 8-10 seconds CP (creatine phosphate) regenerated during resting conditions (ATP + C ? CP + ADP) 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

44. Long-Term Energy Needs 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

45. Fatigue Progressive weakness from use ATP synthesis declines as glycogen is consumed Sodium-potassium pumps fail to maintain membrane potential and excitability Lactic acid buildup inhibits enzyme function Accumulation of extracellular K+ hyperpolarizes the cell Motor nerve fibers use up their acetylcholine

46. Oxygen Debt Vigorous exercise causes dramatic changes in muscle chemistry For a muscle to return to a resting state: Oxygen reserves must be replenished Lactic acid must be converted to pyruvic acid Glycogen stores must be replaced ATP and CP reserves must be resynthesized Oxygen debt � the extra amount of O2 needed for the above restorative processes

47. Begins immediately after activity ends Oxygen debt (excess post-exercise oxygen consumption) Amount of oxygen required during resting period to restore muscle to normal conditions Recovery period

48. Endurance Ability to maintain high-intensity exercise for >5 minutes: determined by VO2 max or Maximal oxygen uptake maximum capacity of an individual's body to transport and utilize oxygen during incremental exercise Measured as the millilitres of oxygen per kilogram of bodyweight per minute (ml/kg/min) average young untrained male will have a VO2 max of approximately 3.5 litres/minute and 45 ml/kg/min Miguel Indurain is reported to have had a VO2 max of 88.0 at his peak average young untrained female will score a VO2 max of approximately 2.0 litres/minute and 38 ml/kg/min To calculate yours go to: http://health.drgily.com/walking-test-peak-aerobic-capacity.php Nutrient availability

49. Types of Skeletal Muscle Fibers Skeletal muscle cells are specialized into 2 main types in humans and primates Specialization allows either High work rates (power output) Long duration contractions 2 cell types are differentiated on whether gene for a slow or fast myosin isoenzyme is expressed in the cell i.e. cell will have a moderate or a high ATPase activity or recycling time

50. Muscle Performance: Types of skeletal muscle fibers Slow-twitch or high-oxidative Contract more slowly Moderate power output Consume ATP at moderate rates High capillary density (rich blood supply) More mitochondria Smaller in diameter Minimize diffusion distances for oxygen and nutrients Large amount of myoglobin. More fatigue-resistant than fast-twitch If blood supply adequate, great endurance Postural muscles, more in lower than upper limbs. Dark meat of chicken.

51. Slow and Fast Fibers Fast-twitch or low-oxidative Respond rapidly to nervous stimulation Maximal ATP consumption can be met only by glycolysis Contain myosin that can break down ATP more rapidly than that in slow-twitch fibers Less blood supply (paler in color) Fewer and smaller mitochondria than slow-twitch Fatigue rapidly as glycogen is depleted Lower limbs in sprinter, upper limbs of most people White meat in chicken. Distribution of fast-twitch and slow-twitch Most muscles have both but varies for each muscle

53. Strength and Conditioning Strength of contraction muscle size and fascicle arrangement 3 or 4 kg / cm2 of cross-sectional area size of motor units and motor unit recruitment length of muscle at start of contraction Resistance training (weight lifting) stimulates cell enlargement due to synthesis of more myofilaments Endurance training (aerobic exercise) produces an increase in mitochondria, glycogen and density of capillaries Atrophy: decrease in muscle size

54. Smooth Muscle Composed of spindle-shaped fibers with a diameter of 2-10 ?m and lengths of several hundred ?m Often organized into two layers (longitudinal and circular) of closely apposed fibers Found in walls of hollow organs (except the heart)

55. Microscopic Anatomy of Smooth Muscle SR is less developed than in skeletal muscle and lacks a specific pattern T tubules are absent There is no troponin complex Plasma membranes have pouchlike infoldings called caveoli Ca2+ is sequestered in the extracellular space near the caveoli, allowing rapid influx when channels are opened There are no visible striations and no sarcomeres Thin and thick filaments are present

56. Thick filaments have heads along their entire length There is no troponin complex Thick and thin filaments are arranged diagonally, causing smooth muscle to contract in a corkscrew manner Noncontractile intermediate filament bundles attach to dense bodies (analogous to Z discs) at regular intervals Proportion and Organization of Myofilaments in Smooth Muscle

57. Proportion and Organization of Myofilaments in Smooth Muscle

58. Stimulation of Smooth Muscle Involuntary and contracts without nerve stimulation Hormones, CO2, low pH, stretch, O2 deficiency Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesicles stimulates multiple myocytes at diffuse junctions

59. Innervation of Smooth Muscle

60. Contraction of Smooth Muscle Whole sheets of smooth muscle exhibit slow, synchronized contraction They contract in unison, reflecting their electrical coupling with gap junctions Action potentials are transmitted from cell to cell Some smooth muscle cells: Act as pacemakers and set the contractile pace for whole sheets of muscle Are self-excitatory and depolarize without external stimuli

61. Contraction Mechanism Actin and myosin interact according to the sliding filament mechanism The final trigger for contractions is a rise in intracellular Ca2+ Ca2+ is released from the SR and from the extracellular space Ca2+ interacts with calmodulin and myosin light chain kinase to activate myosin

62. Role of Calcium Ion Ca2+ binds to calmodulin and activates it Activated calmodulin activates the kinase enzyme Activated kinase transfers phosphate from ATP to myosin cross bridges Phosphorylated cross bridges interact with actin to produce shortening Smooth muscle relaxes when intracellular Ca2+ levels drop See Fig 9.24 in text

63. Response to Stretch Smooth muscle exhibits a phenomenon called stress-relaxation response in which: Smooth muscle responds to stretch only briefly, and then adapts to its new length The new length, however, retains its ability to contract This enables organs such as the stomach and bladder to temporarily store contents

64. Hyperplasia Certain smooth muscles can divide and increase their numbers by undergoing hyperplasia This is shown by estrogen�s effect on the uterus At puberty, estrogen stimulates the synthesis of more smooth muscle, causing the uterus to grow to adult size During pregnancy, estrogen stimulates uterine growth to accommodate the increasing size of the growing fetus

65. Types of Smooth Muscle: Single Unit The cells of single-unit smooth muscle, commonly called visceral muscle: Contract rhythmically as a unit (as one) Are electrically coupled to one another via gap junctions Often exhibit spontaneous action potentials Are arranged in opposing sheets and exhibit stress-relaxation response

66. Types of Smooth Muscle: Multiunit Multiunit smooth muscles are found: In large airways to the lungs In large arteries In arrector pili muscles Attached to hair follicles In the internal eye muscles Multi-unit smooth muscle cells are innervated by more than one motor neuron