Lecture 11- Excitation-Contraction Coupling

Question 1

What is the sarcolemma?

Answer 1

The membrane that wraps around a muscle cell

Question 2

What is the myofibril?

Answer 2

These are what myofilaments (actin + myosin) bundle together to make

Question 3

What is the sarcoplasmic reticulum?

Answer 3

A membrane bound space that is part of the signaling network and has a high concentration of calcium ions. This creates a concentration gradient between the SR and cytoplasm of the muscle cell (vital).

Question 4

What are the two main myofilaments in muscle cells? What does their arrangement cause?

Answer 4

• Actin(thin) +myosin (thick)
• Their parallel arrangement causes striations
• These are the filaments invovled in excitation-contraction coupling and thus generate force

Question 5

What are T-Tubules?

Answer 5

• Extend off the sarcolemma (cell membrane)
• It ensures that as the signal moves along the sarcolemma it can also move deep into the muscle cell to reach myofilaments. If the signal has to diffuse down then myofilaments close to the cell’s surface would contract first and coordinated action would not be possible.

Question 6

What important organelle is in skeletal muscle and is viewed as the ‘power house’? Are numbers consistent throughout all cells?

Answer 6

• The mitochondria

- No, numbers vary depending on the location and function of the particular cell.

Question 7

In excitation-contracting coupling what are the two events which are occuring?

Answer 7

• Excitation= movement of the electrical signal

- Contraction= physical action

Question 8

Why are there voltage gated sodium channels in the T tubules?

Answer 8

It keeps the electrical signal going as sodium comes in causing further depolarization/ ensures that the signal reaches myofilaments (actin + myosin) that are deep in the cell

Question 9

What is the role of the interaction between the voltage sensor (DHPR) and Ryanodine receptor (RyR) in excitation-contraction coupling?

Answer 9

• The voltage sensor spans the gap between inside of T tubule and the muscle cell
• It’s job is to sense the voltage change/ Depolarisation in the tubule and interact with the ryanodine receptor (RyR) on the sarcoplasmic reticulum.
• Once this occurs the RyR will open and passively let calcium diffuse down its concentration gradient through channels from inside the sarcoplasmic reticulum to the cytoplasm of the muscle cell.

Question 10

What is the role of SERCA in excitation-contraction coupling?

Answer 10

It actively pumps calcium into the sarcoplasmic reticulum using ATP in order to create the calcium gradient required between the sarcoplasmic reticulum (high) and muscle cell cytoplasm (low). Means the diffusion out of the ryanodine receptor can be passive.

Question 11

What happens to the calcium that diffuse out of the sarcoplasmic reticulum as a result of the interaction between the voltage sensor (DHPR) and the ryanodine receptor?

Answer 11

It travels and binds to the myofilaments in order to initiate the contraction part of excitation- contraction coupling (cross bridge cycle)

Question 12

What 2 gradients are working to move calcium out of the sarcoplasmic reticulum (once interaction occurs)?

Answer 12

• Concentration gradient set up by SERCA

- Electrical gradient (Highly positive inside and negative/ less positive outside= opposites attract!)

Question 13

In the autoimmune disease Myasthenia gravis, a rapid
and prolonged sequence of action potentials at the
neuromuscular junction (NMJ) will initiate progressively
weaker muscle contractions BECAUSE more
acetylcholine is released from the neuron during each
successive action potential.

For the following question, select:
(A) if both statements (the one before and the one after ‘BECAUSE’)
are true, and are causally related (the fact presented in the first
statement is a result of the fact presented in the second statement)
(B) if both statements are true but are not causally related
(C) if the first statement is true and the second is false
(D) if the first statement is false and the second is true
(E) if both statements are false

Answer 13

C) If the first statement is true and the second is false

Question 14

How is the myosin head different in it’s two states?

Answer 14

• When not activated= tilted

- When activated by ATP= straight/ energized and ready to do pulling action

Question 15

What is tropomyosin?

Answer 15

Filament that wraps around actin

Question 16

What is Troponin?

Answer 16

Complex of proteins associated with tropomyosin

Question 17

In low calcium concentrations what is tropomyosin’s role?

How does this contrast in high calcium concentrations?

Answer 17

• In low calcium concentrations tropomyosin blocks the sites on actin at which myosin can bind therefore preventing cross bridge formation.
• In high calcium concentrations calcium binds to troponin changing its shape and therefore because of it’s association with tropomyosin causing tropomyosin to move out of the way. Myosin can now bind to actin and cross-bridges can form.
• Calcium is therefore essential!

Question 18

What are the steps for the cross-bridge cycle?

Answer 18

• An energized myosin is when ADP and phosphate are bound to it’s head. When activated the head will be up and ready to interaction with binding sites on the thin filament actin.
• If calcium concentrations are low these binding sites will be covered by tropomyosin preventing cross bridge formation, conversely if calcium concentration is high it will bind to troponin and tropomyosin will be forced to move out of the way. (myosin head can now bind to actin)
• Once bound ADP and phosphate will be released causing the myosin head to flex and resulting in contraction/ pulling
• After this point the myosin head becomes relaxed again and ATP binds to detach it
• ATP will then be hydrolyzed to ADP and phosphate energizing the myosin head again to allow for the cycle to start again (myosin bind to actin)

Question 19

In the cross bridge cycle what happens if there is no ATP to bind?

Answer 19

The head of myosin does not detach from actin and have stiffness/ rigor mortis

Question 20

What is the shortcut to the cross-bridge cycle and what does it allow?

Answer 20

• If calcium levels remain high then can skip the relaxation state and just have ADP bind straight back onto actin binding sites (don’t have the period where they are covered by tropomyosin).
• This is important for times where need to generate a lot of force at once e.g. lifting something heavy. Just get continued release of calcium from SR so can keep cross bridge cycle going.