I. Muscle System Overview -
   A) Major functions:
      1) movement
      2) control of organ & blood vessel size
      3) stabilize body position
      4) thermogenesis
   B) Muscles only act by contraction:
   C) Three major muscle types (review these):
      1) skeletal
      2) cardiac
      3) smooth

II. Anatomy of Skeletal Muscles -
   A) Structural hierarchy of muscle
      1) muscle as an organ
         a) covered in fascia (superficial or deep)
         b) wrapped in epimysium
         c) a muscle is a bundle of fascicles
      2) fascicles
        a) wrapped in perimysium
        b) a fascicle is a bundle of muscle fibers
     3) fibers
        a) wrapped in endomysium
        b) membrane of muscle fiber = sarcolemma
        c) cytosol inside muscle fiber = sarcoplasm
        d) a fiber is a bundle of myofibrils
     4) myofibrils
        a) myofibrils are composed of filaments
     5) filaments
        a) thick filaments
            i) thick filaments composed mostly of myosin
        b) thin filaments
            i) thin filaments composed mostly of actin, troponin & tropomyosin
        c) thick and thin filaments arranged in overlapping patterns termed "sarcomeres"
     6) sarcomeres
        a) basic contractile unit of muscle

III. Neuromuscular Communication -
  A) Motor neurons innervate muscle tissue
  B) Motor unit
     1) one motor unit and all muscle fibers it stimulates
     2) from as few as 2-3 fibers/unit (fine control) or 2000/unit (large power movements)
  C) Neuromuscular junction (NMJ)
     1) axon terminals and synaptic end bulbs of motor neuron
     2) synapse
        a) synaptic vesicles in end bulbs containing neurotransmitters (acetylcholine)
        b) synaptic cleft
        c) motor end plate bearing acetylcholine (Ach) receptors
  D) Events of synaptic communication
     1) neuronal action potential arrives at axon terminals
     2) synaptic vesicles release Ach into synaptic cleft
     3) Ach binds to Ach receptors
     4) Ach receptors initiate new action potential on muscle fiber sarcolemma
     5) acetylcholine esterase (AchE) in synaptic cleft is always present to remove XS Ach
  E) Toxins affecting NMJ
     1) cobra toxin and curare
        a) block Ach receptors
        b) cause flaccid paralysis, potentially fatal respiratory arrest
     2) nerve gas and insecticides
        a) inhibit AchE
        b) cause potentially fatal paralytic convulsions
     3) botulism toxin
        a) block Ach release
        b) cause flaccid paralysis; potentially fatal respiratory arrest
     4) tetanus toxin
        a) cause excessive Ach release from motor neurons
        b) cause potentially fatal paralytic convulsions ("lockjaw")
  (for more info on neurotoxins )

IV. Anatomy of Skeletal Muscle Fiber -
  A) Light bands (I)
  B) Dark Bands (A)
  C) Z discs
  D) Myofibrils
     1) forms basic elements of contraction
      2) 3 types of filaments make myofibrils
          a) thick filaments
          b) thin filaments
          c) elastic filaments
      3) sarcomere = overlapping arrangements of filaments
          a) basic unit of contraction
          b) bounded by Z discs

V. Sarcomere Structure -
  A) Thick filaments
      1) mostly myosin protein
          a) ~200 twisted myosin proteins form thick filament ("golf clubs")
          b) held in place by elastic filament (titin protein)
          c) can bind ATP
          d) splits ATP to ADP
          e) can bind actin proteins
  B) Thin filaments
      1) Actin protein
          a) "bean-shaped" protein in strands
          b) has myosin-binding site
      2) Tropomyosin
          a) covers myosin-binding site
      3) Troponin
          a) can bind calcium
          b) regulates action of tropomyosin
  C) Contractile proteins
      1) actin & myosin
  D) Regulatory proteins
      1) troponin & tropomyosin
  E) Events of Muscle Contraction
      1) arrival of neuronal action potential at neuromuscular junction
      2) release and diffusion of acetylcholine into synaptic cleft
      3) binding of acetylcholine to receptor at motor end plate
      4) activation of action potential on muscle surface (sarcolemma)
      5) release of calcium from sarcoplasmic reticulum inside muscle fiber
      6) binding of calcium to troponin/tropomyosin complex
      7) exposure of myosin-binding site on actin
      8) binding of actin and myosin and "Power stroke" single ratchet of myosin to pull actin and release ADP
      9) myosin releases actin, swivels back, binds and splits ATP ("reset")
      10) repeat binding myosin to actin (Repeat step 8-10)

VI. Energy Metabolism in Skeletal Muscle -
  A) Creatine-phosphagen system
      1) uses creatine phosphokinase (CPK or CK)
          a) CPK-MM in skeletal muscle
          b) CPK-MB in cardiac muscle
      2) delivers ~ 30 sec max. activity
  B) Lactic acid pathway (glycolytic pathway)
      1) anaerobic use of glucose (glycolysis mainly)
      2) 2ATP/glucose
      3) lactic acid waste product
      4) can be "recycled" by liver
  C) Aerobic respiration (oxidative) pathway
      1) most efficient use of glucose
      2) 36ATP/glucose
      3) requires oxygen
      4) occurs in mitochondria
  D) Sources of glucose
      1) blood glucose
      2) stored glycogen
  E) Sources/carriers of oxygen
      1) hemoglobin
      2) myoglobin
  F) Recovery oxygen consumption
      1) due to increased metabolic rate and continued use
      2) lactic acid can be recycled in liver
          a) 4 lactic acid converted to glucose, 1 converted to carbon dioxide

VII. Three Main Types of Skeletal Muscle Fibers -
  A) Slow twitch oxidative fibers(I)
      1) oxidative
      2) very fatigue resistant
      3) postural muscles
  B) Fast twitch - A (II-A)
      1) oxidative
      2) rapid contractions
      3) relatively fatigue resistant
      4) sprinter's legs
  C) Fast twitch - B (II-B)
      1) glycolytic
      2) rapid contractions
      3) easily fatigued
      4) arm muscles
  D) Effects of conditioning
      1) mainly II-B to II-A conversions
          a) isotonic contractions (full motions)
                i) concentric contraction = muscle fiber shortens during contraction
                ii) eccentric contraction = muscle fiber lengthens during contraction
      2) increase II-B fiber size
          a) isometric contractions (little change in fiber length with tension)
      3) anabolic steroids
          a) lipid hormones
          b) stimulate fibers to increase protein filaments production
          c) may stimulate "satellite"cells to mature

VIII. Muscle Tension -
  A) All-or-nothing contraction
  B) Factors affecting muscle contractile force
      1) # muscle fibers contracting
      2) rate of motor neuron firing
      3) optimal starting sarcomere length
          a) 70-130% sarcomere length
  C) Rate of motor neuron firing
      1) typical myogram wave
          a) latent period
          b) contractile period
          c) relaxation period
          d) refractory period
      2) "wave summation"
          a) frequent stimulation of fiber increases contractile force (staircase or "treppe" effect)
          b) too much causes tetanus (incomplete=20 to 30/sec; complete=80-100)

IX. Muscular Disorders -
  A) Myasthenia gravis(very good collection of MG Information here)
      1) progressive skeletal weakness
          a) face/neck muscles affected first
                i) "ptosis" droopy eyes
          b) progressive - spreads to include chest & limbs
          c) usually not fatal (5-10% respiratory failure)
      2) affects females 2X males
      3) autoimmune disorder
          a) anti-AchR autoantibodies
          b) loss of AchR in motor end plate
          c) inability to stimulate muscles
      4) neostigmine (AchE inhibitors)
      5) prednisone (immunosuppressive)
      6) plasmaphoresis (filter out anti-AchR)
  B) Muscular Dystrophy(see Muscular Dystrophy on OMIM)
      1) progressive muscle degeneration/atrophy
          a) appears early (3-7 yrs old)
          b) facial & cardiac muscles usually affected last
          c) continuous progression of degeneration
                i) average lifespan about 20yrs
          d) many forms of MD
                 i) Duchenne MD (DMD) more severe form
                 ii) Becker MD milder than DMD
      2) Duchenne MD - most common form
          a) X-linked inherited disorder
          b) most common in boys
          c) caused by defective dystrophin gene
                i) results in continual Ca+ leakage from S.R
                ii) XS Ca+ activates degradative enzymes inside fibers
                iii) muscle fibers degenerate from within
          d) use of gene therapy to replace dystrophin show promise
                i) still problems of keeping transplanted cells in muscle (*article)
          e) detect increased CPK-MM in plasma of MD patients (indicates skeletal muscle damage)
          f) can screen for mutated gene in amniocytes of fetus
  C) Fibromyalgia (for more information)
      1) non-inflammatory painful disorder of musculoskeletal system (or connective?)
          a) more common in females (15X) than males
          b) severe morning pain & stiffness in limbs
          c) several characteristic "tender spots" key to diagnostic features
                i) distal to humeral epicondyles
                  ii) inferior to patella
                iii) 2nd rib costal cartilage
          d) overall fatigue, restlessness, pains
      2) unknown cause
      3) typically treat with NSAIDs
          a) asprin, acetaminophen, ibuprofen
  D) Sprain
      1) overstretched or torn ligaments
  E) Strain
      1) overstretched or torn muscle or tendon
  F) Muscle "cramps"
      1) prolonged involuntary painful contractions
  G) Tremors
      1) involuntary contractions of opposing muscle groups

X. Aging and Muscles -
  A) General skeletal muscle fiber atrophy with age
      1) less myoglobin, mitochondria, fibrils, glycogen, ATP synth/ muscle fiber
      2) less blood flow
      3) less elasticity
          a) increased fibrosis in muscles (accumulation of fibrous connective tissue)
      4) more rapid fatigue
      5) less heat dissipation from skin (overheating)
      6) less satellite cells to help recover from injury
      7) 30-50% decline in muscle performance by age 65
          a) rate of decline mostly constant
          b) conditioning affects the duration of "quality" performance, not rate of decline