Skeletal Muscle Cell Biology

Question 1

What are the 4 basic tissues?

Answer 1

Nervous, epithelial, Connective tissue and muscle

Question 2

WHat are the 3 different types of muscle and which types are volunturay vs involuntary?

Answer 2

skeletal=voluntary

cardiac =involuntary

smooth=involuntary

Question 3

what are skeletal muscle cells called?

Answer 3

muscle fibers, myocytes

Question 4

describe the structure of skeletal muscle

*

Answer 4

highly strucutered in a hierarchical fashion

• gross muscle
  
  • fasicles
    
    • myocytes
      
      • myofibrils
        
        • myofilament

Question 5

how many nuclei do skeletal myocytes have?

Answer 5

100s of nuclei at cell periphery, if in the center=pathology

Question 6

What are the 3 layers of CT investing skeletal muscle

Answer 6

epimysium (deep fascia): entire muscle

perimysium: invests fasicles (groups of myocytes. continuous wiht the CT at the myo-tendon junction

Endomysium: invests individual myoctes, adjacent to basal lamina

Question 7

WHat is the unit of contraction and what is seen on light microscopy for muscle

Answer 7

• Z lines demarcate the sarcomere which is the unit of contraction. Z line to Z line.
• Z lines connect I bands
• Nuclei are peripheral
• striated: alternating A bands (dark) and I bands (light)

Question 8

WHat bisects the I band? What bisects the A band?

Answer 8

I band: Z line

A band: bisected by H-zone/M-line (contains MM-CK)

Question 9

What do myofibrils contain?

Answer 9

Myofibrils contain myofilaments

• Thick and thin
  
  • Thick: A-bands only
    
    • myosin
  • THin: I-bands and A-bands
    
    • actin, 3 troponins, tropomyosin

Question 10

What are T tubules and what is SR?

Answer 10

T (transverse) tuules: invaginate “sarcolemma”

SR=sarcoplasmic reticulum envelopes each myofibril

perpendicular to eachother

Question 11

What is the strucutre of a Neuromuscular (myoneural) Junction Component?

• pre-synaptc
• cleft
• post-synaptic

Answer 11

• Pre-synaptic
  
  • Ca chananels
  • synaptic vesiles (with Ach)
• Cleft: AchE
• Post-synaptic:
  
  • AcHRs facing the cleft
  • Na channels in folds (Ach binds, Na channel open and depolarization occurs)

Question 12

How does an NMJ propogate action potential?

Answer 12

• nerve AP leads to Ca entering the neuron
• synaptic vesicle fuses to pre-synaptic membrane
• Ach is released into cleft
• Ach binds AchReceptor on myocyte
  
  • the above actions are cblocked by succinylcholine or by curariform drugs
• Na enters myocyte which leads to muscle AP

Question 13

How does skeletal muscle excitation occur?

Answer 13

depolarization of the T tubules releases Cav1.1 which then binds RyR in SR membrane which leads to Ca efflux from the SR into the cytoplasm of the skeletal muscle cell. when Ca levels are higher in the skeletal muscle then contraction can occur.

Question 14

How does contraction occur?

Answer 14

• Ca binds troponin C which causes tropomyosin to move out of the way.
• ATP i shydrolyzed to ADP and Pi and myosin binds actin
• a power stroke occurs, when thin filaments move into the A-band and the sarcomere shorts. this is contraction

Question 15

How does the length of the A band change during contraction? How about the length of th I band?

Answer 15

length of the A band is uncahnged

length of the I band is shortened

Question 16

How does muscle relaxation occur?

Answer 16

• Ca is pumped back into the SR via SERCA. this rewuires phospholamban phosphorylation (phospholamban binding inhibits SERCA; but when phosphoplamaban in phosphorylated it dissociates itself from SERCA freeing SERCA)

Question 17

WHat is rigor mortis?

Answer 17

in the absence of ATP, myosin stays bound to actin; therefore relxation cant occur, hence “stiffening” occurs

Question 18

What is malignant hyperthermia and what causes it ?

Answer 18

• volatile anesthetics
• gain of funtion gene mutations
  
  • CACNA1S gene (encodes Cav1.1)
  • RYR gene (encodes ryanodine receptor)
    
    • RYR=Ca channel in SR that promotes Ca release
• intervention: dantrolene
  
  • muscle relaxant; inibits Ca release via RYR

Question 19

WHat is the thick to thin myofibril ratio?

Answer 19

6:1

Question 20

What are “slow twitch” muscle fibers

Answer 20

• continous contraction (oxidative) aerobic
  
  • red fibers: due to enrichment of myoglobin and mitochondria
  • generates ATP from serobic respiration
  • susbstrate fatty acids
  • used by marathoners

Question 21

WHat are type II fibers?

Answer 21

“fast twitch” glycolytic

• white fibers due to enrichemnet of glycogen
• generates ATP from anaerobic glycolysis
• susbstrae: glycogen
• used by sprinters
  *

Question 22

where can energy for muscle contrction be derived from besides aerobic and anaerobic respiration?

Answer 22

creatine phosphate

Question 23

what are satellitle cells?

Answer 23

aka skeletal myoblasts

• adult stem cells
• reside in a “niche” inbetween sarcolemma (cell membrane) and basal lamina
• activated from Go after insult to basal lamina

Question 24

skeletal muscle can regenerate the whole muscle. How does this occur?

Answer 24

1. Insult: damage to basal lamina
2. Proliferation of “satellite cells”
   
   1. satellite cells released from injured basal lamin and they proliferate
   2. compete with invadinf fibroblasts
3. clone: daughter cells cease mitosis
4. Fusion: myotube formation (immature muscle cells)
5. day 21 there are new skeletal muscle cells

Question 25

What is myostatin?

Answer 25

• growth factor secreted by skeletal myocytes
• inhibits satellitle cell proliferation
  
  • likely via up-regulation of p21
  • KO of myostatin gene=skeletal muscle hypertrophy
  • target for inhibition in muscular dystrophy patients

Question 26

How do you get Duchenne Muscular Dystrophy?

Answer 26

dystrophin mutation.

• treatment: cellular therapy w skeletal myoblasts
• gene therapy w advenovirus-dystrophin cDNA
• drugs
  
  • prednisone
  • PTC 124
  • gentamicin
  • OdN