Skeletal Muscle; Neuromuscular Junction

Question 1

What are the main components of the neuromuscular junction?

Answer 1

1. VGNa⁺ channels carry AP down membrane
2. VGCa²⁺ channels open -> Ca²⁺ increases
3. Vesicles empty contents into the synaptic cleft
4. NT binds to receptor on postsynaptic cell
5. Na⁺ entry
6. Action potential propagation along muscle fiber
7. Stimulation leads to end plate potential (EPP)

Question 2

Once end plate potential has occured, how does the action potential move down the t-tubules?

Answer 2

Action potential travels down the sarcolemma and down t-tubules

Actvates DHPRs -> activate RyR to release Ca²⁺

Calcium induces muscle contraction via actin/myosin interaction

Question 3

How is skeletal muscle organized to result in contraction?

Answer 3

• In each contracting unit, or sarcomere, thin actin and thick myosin filaments are juxtaposed, but cannot interact in the absence of calcium.
• This is because myosin binding sites on the actin filaments are all covered by a rod-shaped protein called tropomyosin. A calcium-sensitive complex called troponin is attached to each end of the tropomyosin molecule
• When calcium floods the cell, troponin binds to it moving tropomyosin off the myosin-binding sites.
• Opening the myosin-binding sites on the actin filaments allows the myosin motors to crawl along the actin resulting in the contraction of the muscle fiber.
• Calcium is then quickly returned to the sarcoplasmic reticulum by the action of a calcium pump.
• Without calcium, myosin releases actin, and the filaments slide back to their original positions.

Question 4

Explain the hydrolysis of ATP and the powerstroke

Answer 4

Question 5

What is the sliding filament theory, and what changes occur during contraction?

Answer 5

In a fully contracted muscle unit:

• H zone disappears
• I band disappears

This is due to overlap between the actin and myosin. Because the thin actin filaments have overlapped there is a reduced potential for cross bridges to form again.

Question 6

What is the length-tension relationship?

Answer 6

At optimal overlap of actin and myosin you can generate the most force

Question 7

How is Ach broken down, synthesized, and packaged?

Answer 7

Question 8

After a contraction has occured, how is is terminated and calcium reuptaken?

Answer 8

NCX
SERCA
Calsequestrin

Question 9

How can a cell increase the force of contraction?

Answer 9

1. Fiber summation -> recruiting more motor units
2. Frequency summation -> of individual fibers

Question 10

Compare and contrast depolarizing MR to non-depolarizing MR

Answer 10

Depolarizing -> succinylcholine (partial agonist)

• activates receptor and maintains depolarization
• causes paralysis, fasciculations, etc.

Non-depolarizing -> antagonist that completely blocks receptor activation
-also resulting in paralysis

Question 11

What is rhabdomyolysis?

Answer 11

When muscles are broken down to overuse

Effects:

• Hyperkalemia
• Hypocalcemia
• Myoglobin released from cell
• Acidosis/aciduria
• Increase in creatine kinase

Symptoms:

• Reddish/brown urine
• Muscle pain/weakness/fatigue
• Can cause kidney damage

Question 12

What is myasthenia gravis?

Answer 12

Autoimmune disease wehre there is antibody production to Ach

Symptoms:
-Weakening of skeletal muscles