Mechanism of muscle contraction & excitation-contraction coupling

Question 1

What are the divisions of the motor nervous system?

Answer 1

1) Autonomic: goes to the glands, cardiac and smooth muscles

2) Somatic: goes to the skeletal muscles

Question 2

Describe the skeletal muscle structure

Answer 2

1) Sarcomere (Actin & myosin)

2) Myofibril

3) Muscle fiber

4) Muscle fiber bundles

5) Skeletal muscles

• Sarcomeres are the basic contractile unit, they are made of >40 proteins but the main ones are the tick myosin in the centre and the thin actin that surrounds it

Question 3

Describe the sarcomere

Answer 3

• A group of proteins between two Z-lines, and their major proteins is actin and myosin
• The actin-myosin binding occurs between the binding site on the G-actin & myosin head
• G-actin is a single molecule of actin, while F-actin is a combination of G-actins
• The actin filament is made of 2 chains of F-actin
• The myosin filaments are a group of up to 200 molecules of myosin, its head has two binding sites one for myosin and the other for ATP
• In a relaxed muscle binding sites of G-actin are covered by tropomyosin

Question 4

What is tropomyosin?

Answer 4

• Filamentous protein that blocks the myosin binding sites on actin
• Troponin is a complex of 3 globular proteins:

1) Troponin T (tropomyosin) attaches the “troponin complex”, to the “tropomyosin” for stabilization

2) Troponin I (inhibition) attaches actin-tropomyosin complex in place for stabilization

3) Troponin-C (Ca+2) binds calcium for the initiation of contraction

• Troponin has multiple isoforms: skeletal, cardiac and smooth muscle isoforms

Question 5

How can we diagnose myocardial infarction?

Answer 5

Injury to the cardiac muscles in a myocardial infarction causes the release of troponins (the cardiac isoform) into the blood, which we can use to diagnose a myocardial infarction

Question 6

What is an example of other proteins found in the sarcomeres?

Answer 6

Titin

• Largest protein in the body 27-33k amino acids
• It give rise to passive tension in contracting muscle fiber

Question 7

What are the different areas in the sarcomere?

Answer 7

A sarcomere is an area between two z-discs

1) I band: The area that contains actin but no myosin found on the edges

2) H zone: The area that contains myosin but no actin found in the middle

3) A band: the area which contains myosin and actin

4) Z disk: The edges of the sarcomere

5) M line: the exact center of a sarcomere

Question 8

Which areas of the sarcomeres shorten when contracting?

Answer 8

H zone & I band

Question 9

What is the pathway to contract our muscles?

Answer 9

• 2 Neurons carry the signal from the PMC to the muscles

1) Primary motor cortex - spinal cord (contralateral “left brain right arm, etc)

• A pathology will occur in case of a stroke or ischemia

2) Spinal cord to skeletal muscles

• A pathology will arise if for example the median nerve is affected

Question 10

How do nerve impulses cause contraction?

Answer 10

• The cell membrane of muscle cells is frequently invaginated inwards forming a structure called T-Tubules which is surrounded by sarcoplasmic reticulum
• The sarcoplasmic reticulum stores calcium
• The T-tubule and the 2 sarcoplasmic reticulum that surrounds it are called a triad

so for example to contract my right elbow:

1) Left primary motor cortex
2) upper motor neuron (spinal cord)
3) Lower motor neuron (spinal cord to skeletal muscle)
4) Reaches the neuromuscular junction
5) At the neuromuscular junction excitation “due to AP generation”-contraction “in the sarcomere” coupling will occur

Question 11

What are the functions of the sarcoplasmic reticulum?

Answer 11

• It is the endoplasmic reticulum of muscle cells

1) Folds & packages proteins (like all endoplasmic reticulums)

2) Stores & releases calcium (unique to sarcoplasmic reticulum) which will bind to troponin C

Question 12

How does the muscle cell get excited?

Answer 12

1) AP arrives at the Neuro Muscular Junction

2) Opening of Ca channels and the influx of calcium

3) Calcium will then bind to the membrane of the synaptic vesicle

4) The synaptic vesicle will fuse with the cell membrane and release acetylcholine

5) Ach will bind to the Ach receptor in the muscle membrane (sarcolemma)

6) Ach binding will open Na channels and generate an action potential in the muscle

7) Ach will be destructed by the acetylcholine enzyme

8) The AP will travel through the whole sarcolemma, once it reaches the T-tubules it will release calcium via ryanodine receptors (RyR)

9) Calcium will then go to bind to the Troponin C (initiation of contraction)

10) Once we are done with contraction via the use of ATP SERCA channels will pump the Ca2+ in the muscles back into the sarcoplasmic reticulum

Question 13

What is the mechanism by which calcium causes muscles to contract?

Answer 13

• Muscle contraction is a result of the attachment and detachment of actin and myosin
• Calcium will bind to troponin-c exposing and binding the myosin to the actin in a locked state
• Then ATP will unlock for the actin to bind to another myosin, contracting the muscles

Question 14

What is meant by rigor mortis?

Answer 14

It is when someone is dead where their myosin head remains attached to actin and the muscle is permanently contracted as there is no ATP

Question 15

What are the different neuromuscular junction pathologies?

Answer 15

• The pathologies are either auto-antibodies (LEMG & MG) or Ach receptor-blocking

1) Lambert eaton myasthenia syndrome (the body releases autoantibodies against Ca channels)

2) Botulinum toxin (blocks the release of Ach)

3) Myasthenia gravis (auto-antibodies against Ach receptors in the sarcolemma

4) Recuronium (Blocks Ach receptor) used as an anesthetic

5) Krait venom (block Ach receptor)

6) Saw scaled viper

Question 16

What are the temporal events during excitation-contraction coupling?

Answer 16

1) Action Potential (Na channel opening in sarcolemma)

2) Release of Ca2+ from SR by RyR

3) Force generation: due to the attachment and detachment of actin and myosin in the sarcomere

Question 17

What parts of the muscle fibers require energy to work?

Answer 17

1) Na/K ATPase pump (maintains the resting membrane potential via pumping Na out and K in acter the AP is done

2) Myosin ATPase (releases the myosin from actin during contraction)

3) SERCA ATPase pump (pumps Ca into the SR after contraction)

Question 18

Where does the energy come from (sources of ATP)?

Answer 18

1) Phosphocreatine (lysis of phosphocreatine) = creatine + phosphate, where the released phosphate is used to convert ADP into ATP “fastest ATP source”

2) Glycogen (glycolysis) = lactic acid

3) Glucose/Fatty acids/ Amino acids (oxidative phosphorylation = CO2 + H2O + Urea

Question 19

What is the order of energy utilization when we start running?

Answer 19

1) Phosphocreatine (lasts up to 10 seconds)

2) Glycolysis (lasts 60-90 seconds)

3) Oxidative phosphorylation (lasts hours)

Question 20

What are the different types of muscle fibers?

Answer 20

1) Type I (slow-oxidative) slow and need long-term energy “oxidative phosphorylation” for holding objects, endurance activities (repeated, prolonged contractions)

2) Type 2a (fast-oxidative)

3) Type 2b (fast glycolytic) (for jumping, lifting sprinting, short, powerful contractions, and rapid movements)

• Small animals have more type 2b while large animals have more type 1
• Type 2 fibers can change size depending on our activity while type one usually do not

Question 21

What structures are more abundant in type 1 fibers compared to type 2b?

Answer 21

It has an increased number of:

1) Myoglobin
2) Mitochondria
3) Capillaries

Type 2b is higher in all other parameters

1) SERCA ATPase activity
2) size and strength of muscle fiber
3) speed of action potential in motor axon
4) Speed of contraction
5) Glycogen content

Question 22

What are the different durations of muscle contraction?

Answer 22

1) Ocular muscle: rapid contraction for rapid eye movement (mainly type 2b fibers) “fast duration”

2) Calf muscles: slow sustained contractions to pump venous blood against gravity (mainly type 1 fibers) “slow duration”

Question 23

Why do our muscles get tired?

Answer 23

1) Peripheral:
- Depletion of ATP
- Depletion of glycogen
- Accumulation of lactic acid
- Increased ADP (interferes with cross-bridging)

2) Central:
- Reduced activation of motor neurons
- Psychological