Block IV: Membrane systems SM, calcium, myosin contractile cycle

Question 1

What are the membrane systems present in skeletal muscle?

Answer 1

T-tubules
Sarcoplasmic reticulum (SR)
Triads

Question 2

Where are T-tubules located and their function

Answer 2

tubular invaginations of sarcolemma into cytoplasm at the AI
junction of the sarcomere. In response to depolarization of sarcolemma at neuromuscular junction they carry impulse into muscle cell

Question 3

What is the sarcoplasmic reticulum and what does it do?

Answer 3

specialized smooth endoplasmic reticulum able to store, release, and sequester calcium. Storage of the calcium involves calsequestrin which can bind up to 50 calcium ions

Question 4

What are Triads, its location and function?

Answer 4

specialized regions in which a central t-tubule is flanked by two
terminal cisterna sacs of the SR. This is the site of release of calcium for contraction from the terminal cisterna of the SR

Question 5

identify

Answer 5

Triads

Question 6

identify

Answer 6

T-tubule and Terminal cisterna of SR (stores and releases calcium [contains calsequestrin])

Question 7

What is the Smooth Endoplasmic Reticulum Calcium ATPase (SERCA)?

Answer 7

calcium pump in a network of SR tubules near the center of the sarcomere near the M-band. It pumps calcium from
the cytoplasm back into sarcoplasmic reticulum and back
to the terminal cisterna

Question 8

What happens when calcium is sufficiently removed from cytoplasm?

Answer 8

the contraction of the skeletal muscle will stop until the next cycle of depolarization of the sarcolemma occurs

Question 9

What is the system of membranes and triads important?

Answer 9

The extremely large size of the skeletal muscle fiber means that diffusion of calcium from the plasma membrane into the cell would be far too slow to allow a synchronous contraction of the sarcomeres and myofibrils at the center of the skeletal muscle fiber with those at the surface.

The elaborate system of membranes and triads at the level of each sarcomere assures that all sarcomeres in the skeletal muscle fiber contract at almost identical times

Question 10

Regulation of contraction is controlled by?

Answer 10

Calcium concentration in the cytoplasm

Question 11

Which mechanisms does regular contraction and the calcium concentration involve?

Answer 11

Excitation Contraction Coupling Mechanism
The Steric Blocking Mechanism of Calcium Regulation
Sliding filament mechanism of contraction

Question 12

What does Excitation Contraction Coupling Mechanism do?

Answer 12

which couples the nerve stimulation at the muscle cell surface to the release of calcium into the cytoplasm. This involves specialized membranes – the sarcoplasmic reticulum and the T-tubule which form a structure called the triad that surrounds each sarcomere insuring simulataneous release of calcium all through out the large skeletal muscle fiber

Question 13

What does The Steric Blocking Mechanism of Calcium Regulation do?

Answer 13

at the level of the thick and thin filaments to initiate contraction upon release of high levels of calcium

Question 14

what does Sliding filament mechanism of contraction do?

Answer 14

thick and thin filaments slide past each other to produce shortening of the sarcomere

Question 15

In the excitation contraction coupling mechanism what are the voltage sensor proteins and when are they activated?

Answer 15

The T-tubule contains voltage-sensor proteins called dihydropyridine-sensitive receptors (DHSRs), which are depolarization-sensitive transmembrane channels that are activated when the plasma membrane depolarizes.

Question 16

What affects the gated Ca+2 relase channels (RyR1 isoform of ryanodine receptors)?

Answer 16

Confromational changes of DHSRs affect gated Ca+2-release channels (RyR1 isoform of ryanodine receptors) located in the adjacent membranes of the terminal cisternae of the sarcoplasmic reticulum causing release of calcium into the cytoplasm to bind to
thin filament and initiate contraction

Question 17

What happens in the absence of calcium in the steric blocking mechanism of calcium regulation vs in the presence of calcium?

Answer 17

In the absence of calcium the troponin-tropomyosin complex blocks the binding site (yellow in diagram) for myosin on actin

Upon release of calcium from the terminal cisterna of SR , calcium
binds to troponin causing the troponin-tropomyosin complex to shift its position, thus exposing the binding site for myosin and allowing the myosin head to bind to actin and initiate contraction

Question 18

Explain the sliding filament mechanism of muscle contraction (isotonic)

Answer 18

During contraction the myosin heads on the thick filament reach out to adjacent actin thin filaments, bind, and undergo a power stroke to pull the thin filaments in towards the center of the sarcomere. The result is a shortening of the sarcomere by relative sliding of the two filament arrays

The thick filaments and thin filaments do not change in length. H-band and I-band appear to change in width

Question 19

Explain stage 1 of myosin contractile cycle?

Answer 19

Myosin head bound to the actin in the thin filament. No ATP present. No reattachment at this point. Myosin head remains in rigor conformation until ATP binds

Question 20

Explain stage 2 of myosin contractile cycle

Answer 20

ATP binds to myosin head causing it to detach from actin thin filament

Question 21

Explain stage 3 of myosin contractile cycle

Answer 21

ATP on head is hydrolyzed to bound ADP + Pi. This provides energy for a conformational change in the shape of myosin head

Question 22

Explain stage 4 of myosin contractile cycle

Answer 22

Reattachment of the head to a new actin molecule in the thin filament occurs. This is a weak binding state

Question 23

Explain stage 5&6 of myosin contractile cycle

Answer 23

Pi is released. This causes a strong binding state of the myosin head to the actin of thin filament and triggers a conformational change of the myosin head back to its original shape thus producing the power stroke that generates force and moves the thin filament inward toward the bare zone. ADP is then released & myosin is in rigor position, cycle repeats

Question 24

What are the 3 conditions of the myosin contractile muscle cycle

Answer 24

Relaxation condition
Contraction condition
Rigor condition

Question 25

What is the relaxation condition?

Answer 25

ATP present, but no Ca+2. The myosin heads lie on the filament
backbone not attached to thin filament.

Question 26

What is the contraction condition?

Answer 26

Both ATP & Ca+2 present. The myosin heads attach to thin filament and undergo power stroke.

Question 27

What is the rigor condition?

Answer 27

No ATP present (In death this condition is known as rigor mortis - the stiffening of the body after death). In the absence of ATP the myosin heads remain attached to actin thin filament in what is known as the “rigor” state.