INTS 10: Muscle Contraction, Bone Development, Disease and Injury

Question 1

What are the four major function of the musculoskeletal system?

Answer 1

• producing movement
• maintaining posture
• stabilising joints
• producing heat

Question 2

What are the three types of muscle in the body?

Answer 2

Question 3

What is muscle tissue made up of?

Answer 3

• muscle fibres: multinucleate structures made up of fused muscles cells or myocytes
• associated blood vessels, nerves and connective tissues

Question 4

Describe skeletal muscle structure at a macroscopic level

Answer 4

• at a macroscopic level, skeletal muscle can be seen to be made up of bundles, or fascicles of muscle fibres
• the individual muscle fibres and fascicles are surrounded by layers of connective tissue

Question 5

Describe the structure of the skeletal muscle at the microscopic level

Answer 5

• each muscle fibre is made up of many, many myofibrils, which are the contractile units
• the major constituents of myofibrils are actin and myosin filaments
• myofibrils are arranged into sarcomeres
• the variable appearance of different parts of the sarcomere is the reason that skeletal muscle is striated
• a network of tubules, called the sarcoplasmic reticulum, surrounds myofibrils
• transverse tubules, or T tubules also cross myofibrils and communicate with the sarcoplasmic reticulum
• neuromuscular junctions are the point of communication between the nervous system and the muscular system

Question 6

What are skeletal muscles comprised of?

Answer 6

• skeletal muscles are made up of muscle fibres comprised of fused myocytes
• within the muscle fibres are a large number of myofibrils
• predominantly actin and myosin filaments

Question 7

Why does skeletal (and cardiac) muscle have a striated appearance?

Answer 7

• each muscle fibre is made up of an array of myofibrils
• predominantly actin and myosin filaments
• the arrangement of these fibres into parallel array and the precise overlapping distribution of these myofilaments gives them their striated appearance

Question 8

Describe sarcomere structure and what it is

Answer 8

• a sarcomere is the region between two Z discs
• actin filaments are attached to the Z disc
• myosin filaments are located in the central part of the sarcomere
• actin filaments are also referred to as thin filaments
• myosin filaments are also referred to as thick filaments

Question 9

What parts of the muscle causes contraction?

Answer 9

• muscle contraction occurs through the sliding of actin filaments relative to myosin filaments

Question 10

What is the chain of command for muscle contraction to occur?

Answer 10

Question 11

Describe the spinal motor nerves involved in muscle contraction and their pathway

Answer 11

• motor signals are generated within the sensorimotor cortex in the brain
• signals are relayed to motor neurons within the ventral horn of the spinal cord
• axons from motor neurons exit the spinal cord via the ventral root to join mixed spinal nerves
• these contain both sensory and motor axons
• motor axons travel to muscles all around the body
• each axons will have many axon terminals which make contact with a single myocyte at the neuromuscular junction

Question 12

What is the neuromuscular junction?

Describe its features and their functions

Answer 12

• it is the direct point of contact between the nervous system and the musculoskeletal system
• the axon terminal:
• formed when the myelinated motor neuron axon becomes unmyelinated
• contains vesicles containing acetylcholine (neurotransmitter)
• contain voltage-gated calcium channels
• a synaptic cleft is between the presynaptic membrane of the axon terminal and the postsynaptic membrane (the plasma membrane of the muscle fibre)
• acetylcholine binds cation receptors on the postsynaptic membrane
• the enzyme acetylcholinesterase is located on the postsynaptic membrane

Question 13

Describe the key stages of synaptic transmission at the neuromuscular junction

Answer 13

1. An axon potential is propagated along a motor neuron axon to the axon terminal
2. At the axon terminal, the action potential opens voltage-gated calcium channels and this leads to calcium ion influx into the axon terminal
3. This causes exocytosis of vesicles containing acetylcholine
4. Acetylcholine is released into the synaptic cleft
5. They bind to receptor cation channels on the postsynaptic membrane
   - this leads to the opening of sodium ion channels which allows the influx of sodium ions exceeding the efflux of potassium ions
   - this causes depolarization of the postsynaptic membrane
6. Local current flows between depolarised endplate region and adjacent membrane
7. An axon potential is triggered and is spread along the muscle fibre membrane
8. Finally, acetylcholine is broken down by acetylcholinesterase

Question 14

Describe how muscle is activated once the action potential has been generated

Answer 14

• the action potential is propagated through the transverse tubule (T tubule) network
  1. The action potential propagates along the muscle fibre into the muscle cell
  2. This lead to the release of calcium ions from the sarcoplasmic reticulum (SR)
  3. The calcium ions bind to troponin on actin filaments
  4. This leads to a conformational change in the position of tropomyosin which moves to unblock myosin-binding sites
  5. This allows cross-bridges to form
• which enables the generation of force through the sliding of actin filaments
  6. While an action potential is being generated, this process occurs continuously with Ca²⁺ being actively pumped back into the sarcoplasmic reticulum

Question 15

What is the sliding filament theory?

Answer 15

• this is that muscle contraction results from a shortening of the sarcomere
• occurs when actin filaments move towards the centre of the sarcomere, drawing the associated Z discs toward one another
• this event occurs in a coordinated fashion across the whole muscle to result in force generation

Question 16

What in the myosin filaments allow actin filaments to be pulled toward the middle of the sarcomere?

Answer 16

• there are protrusions from myosin filaments that appear to ‘pull’ the actin filaments
• the protrusions are the heads of the myosin filaments
• the rest is called the tail
• the myosin heads use ATP to attach to actin filaments, which then undergo a conformational change, which provides the force that slides the actin filament towards the middle of the sarcomere
• this process is called the Crossbridge Cycle

Question 17

Describe the Crossbridge Cycle

Answer 17

1. The myosin head binds to ATP
   - this leads to detachment from actin
2. ATP is hydrolysed to ADP + P_i
   - the myosin head is cocked back
3. Crossbridge is formed
   - the myosin head binds to actin
4. ADP and P_i are released
   - power stroke: actin filament slides relative to myosin filament
   - the sarcomere shortens

Question 18

Describe the steps of muscle relaxation

Answer 18

1. The action potential ends when the muscle no longer needs to generate force
2. This stops Ca²⁺ release from the sarcoplasmic reticulum
3. Which also stops its subsequent binding to troponin
4. With no Ca²⁺ bound, tropomyosin moves to block myosin-binding sites
5. The crossbridges detach
6. Ca²⁺ continues to be pumped back into the sarcoplasmic reticulumn, as this is an ATP-driven pump

Question 19

What are the two processes that cause the formation of bones?

Answer 19

• intramembranous ossification
• endochronal ossification

Question 20

Describe intramembranous ossification

Answer 20

• direct bone formation
• flat bones are formed by this process
• e.g. skull, ribs
• their primary function is protection of internal organs
• precursor cells directly differentiate from connective tissue to become osteoblasts (bone-forming cells) and produce the bone

Question 21

What is endochrondral ossification?

How are bones formed in this way?

Answer 21

• this is bone formation from a cartilage model
• most bones are formed from a cartilage model
• bones formed this way are called long bones
• throughout growth they have a cartilaginous growth plate between ossification centers, allowing rapid linear growth of bones
• precursor cells become chondroblasts (cartilage-producing cells)
• they develop a cartilage model of the bones
• as development proceeds, blood vessels invade this cartilage model, bringing osteogenic cells that transform the cartilage model into bone

Question 22

Describe the stages of endochondral bone formation

Answer 22

• Fetal Development:
• initially a cartilage model of the bone is formed
• Newborn Baby:
• the bone shaft (diaphysis) is mostly bone
• the ends (epiphyses) are made of cartilage that gradually calcifies
• the diaphysis arises from the primary ossification centre, usually towards the centre of the bone
• Child:
• the epiphyses contain secondary ossification centres, from which bone forms
• cartilaginous growth plates are present between primary and secondary ossification centres until the bone has reached its mature length
• these are the main sites of bone elongation
• Adult:
• bone growth is usually complete by 20
• the shafts, growth plates and epiphyses has all ossified and fused into continuous bone

Question 23

What is bone remodelling?

Answer 23

• once bones are fully developed, they are not static tissues
• after around 10 teats, our whole skeleton is respaced
• small regions of old or damaged bone are constantly being removed and replaced through a process called bone remodelling
• osteoclasts degrade the old bone
• then osteoblasts replace it with new bone

Question 24

Describe bone cancer

Answer 24

Question 25

Familiarise yourself with the bone disease: postmenopausal osteoporosis

Answer 25

Question 26

Familiarise yourself with the bone disease: osteoarthritis

Answer 26

Question 27

Familiarise yourself with the bone disease: myasthenia gravis

Answer 27

Question 28

Familiarise yourself with the bone disease: muscular dystrophies

Answer 28