6. Skeletal Muscle Structure and the Cytoskeleton

Question 1

skeletal muscle. How many in body? what are they made up of?

Answer 1

660 muscles in the human body

Muscle comprises
75% = H20
20% = Protein
5% 
creatine phosphate 
Urea & lactate
Minerals: calcium, magnesium, and phosphorus 
enzymes
Ions: sodium, potassium, and chloride 
amino acids, fats, and carbohydrates

Question 2

Skeletal muscle makes up…
How much of body weight?
How much of protein in body?
What must a muscle essentially do?

Answer 2

Comprises ~ 40 % of body weight
Contains ~ 50 – 75 % of all proteins in the human body

Essentials of muscle mass (1-2% is catabolized daily)
      Force production (CSA)
       Energy store (aa → Acetyl CoA → OxPhos)
       Nitrogen store (surgery, immune response)

Question 3

Skeletal Muscle Organization

Answer 3

Whole muscle 
        belly	
Muscle fascicle 
        bundle of muscle fibers
Muscle fiber
        muscle cell	
Myofibril  
       sarcomeres in series	
Sarcomere 	
       Z-disc to Z-disc	
Myofilament 
      i.e., actin and myosin

Question 4

sarcomere

Answer 4

Fundamental contractile unit in SM
Defined as the filamentous array between Z-lines
Two predominant filaments
Thin filament = Actin (predominantly)
Thick filament = Myosin (predominantly)

Question 5

muscle fiber

Answer 5

Myofilaments = 80% Vol.
2 major filaments
        Actin
~20% of muscle protein mass
        Myosin
~54% of muscle protein mass

Question 6

OVERVIEW OF MM CONTRACTION:

Answer 6

OVERVIEW OF MM CONTRACTION:
• a-motor neuron → action potential in motor neuron
• AP propagation to pre-synapse → causes opening of Ca++ channels
• Ca++ = vesicle emptying of Ach into synaptic cleft
• Ach diffuses to post-synapse and combines w/ Ach receptor (R’)
• Causes increase in Na+ and K+ permeability = depolarization of mm cell = AP
• AP travels outward in all directions and into T-tubules
• AP propagation into T-tubule diminishes as AP travels further into mm cell
• AP activates DHP (dihdrophyridicine) R’ in T-tubule
• DHP channel is physically connected to Ryanodine R’ (in the SR) and causes it to release Ca++ into cytosol
• Ca++ binds to C-subunit of troponin and moves tropomyosin away from actin (f-actin) binding site
• Myosin immediately attached to actin
• Cross bridge formation = “muscle contraction” w/ presence of ATP

Question 7

Muscular Dystrophies:

Answer 7

• Duchenne’s & Becker’s
• Heterogeneous group of congenital mm diseases = mm weakness & atrophy/destruction of fibers
• Protein players = dystrophin (427 kDa) → dystroglycan complex
• Limb Girdle MD (mm dystrophy) = sarcoglycan complex
• X-linked DCM (cardiomyopathy) = dystrophin
**single protein can cause severe disease/dysfunction
mutations cause fragility w/ repeated contractions