5. Muscle

Question 1

Describe the structure and organisation of the sarcomere

Answer 1

A sarcomere is the distance between Z lines. Uniform length of 2.5 micrometres in relaxed muscle. Contain troponin, Actin (thin filaments), tropomyosin, myosin (thick filaments), titin and nebulin.

• A-bands: This is the darkest of the sarcomere’s bands and encompasses the entire length of a thick filament. At the outer edges of the A-Band, the thick and thin filaments overlap. The center of the A band is occupied by thick filaments only. (A comes from the term anisotropic = an=Not, therefor meaning not light coloured).
• I-Bands: These are the lightest colour bands of the sarcomere and represent a region occupied only by thin filaments. (“I” comes from isotropic, refering to the light coloured filament). A Z-disk runs through the middle of every I band, so each half of an I band belongs to a different sarcomere.
• H-Zone: This central region of the A-band is lighter than the outer edges of the A band because the H zone is occupied by thick filaments only. (H comes from helles, the german word for clear).
• M-Line: This band represents proteins that form the attachment site for thick filaments, equivalent to the Z-disk for the thin filaments. Each M line divides an A band in half. (M is abbreviation for mittle, german word for middle).
• Z-Disc: Zigzag protein structures that serve as the attachement site for thin filaments. (abbreviation Z comes from zwischen, the german word for between).

Question 2

What proteins can be found in each of the following muscle lines/bands: A, I, H, M & Z?

Answer 2

• A-bands: Myosin, Actin, Nebulin and Titin
• I-Bands: Actin, Nebulin and Titin
• H-Zone: Myosin, Actin, Nebulin and Titin
• M-Line: Myosin, Titin
• Z-Disc: Actin, Titin, Nebulin

Question 3

What is/are the functions of the structural proteins of muscle?

Answer 3

• Titin - Elastic Anchor: Spans distance from one Z-disc to neighboring M line.
• Nebulin - Non-Elastic Anchor: Lying along the thin filaements, it attaches to a Z disc but does not extend to the M line.
• Actin - Part of thin filament: Consists of beads known as G-Actin proteins that are strung together to form an F-Actin polymer.
• Troponin - Part of thin filament: Binds with Calcium ions and undergoes conformational change upon nervous impulse.
• Tropomyosin - Part of thin filament: In relaxed muscle it blocks binding sites on actin molecules, preventing crossbridge formation, thus preventing contraction in muscle without nervous impulse.
• Myosin - Part of thick filament: Hydrolyzes ATP to ADP. Myosin traps that released energy and stores it as potential energy in the angle beterrn the myosin heads. Upon nervous impulse the myosin molecules are read to go.

Question 4

Tropomyosin is often “in the groove”; what does this mean?

Answer 4

The space between the actin double helix.

Question 5

How is a nerve AP converted into muscle AP?

Answer 5

• Arrival of a somatic nerve impulse → release of ACh from synaptic vesicles → ACh binds to receptors on muscle motor end plate → opening of sodium gated ion channels → Inside of muscle becomes more positive (depolarisation) → Triggers muscle action potential that will travel over the sarcolemma which will continue within the T-System to ensure simultaneous contraction.

Question 6

Describe the structural relationship between the sarcoplasmic reticulum and the T-tubule system.

Answer 6

The T-Tubule system is the inwardly folded extensions of the membrane of a muscle cell. Located along the T-tubules are voltage sensitive dihydropyrodine (DHP) receptors.

The sarcoplasmic reticulum (SR) is an organelle of the muscle cell, found within the sarcoplasm. The SR is essentially a system of flattened vesicles, which function to store and release calcium ions.

The T-tubule system is mechanically linked to the lateral sacs of the SR by specialised foot proteins, known as Ryanodine receptors (RyR). Specifically, RyR are located on the SR and extend toward the DHP receptors located on the T-tubules.

Question 7

Describe the functional relationship between the sarcoplasmic reticulum and the T-tubule system.

Answer 7

T-Tubules bring AP inside muscle fiber → Release calcium from sarcoplasmic reticulum.

Question 8

Describe in detail what triggers the release of calcium ions from the sarcoplasmic reticulum.

Answer 8

When an impulse arrives at the motor end plate it causes depolarisation of the sarcolemma of the muscle. This depolarisation travels deep throughout the muscle via the T-tubule system. As the action potential spreads down the T-tubules it stimulates voltage sensitive dihydropyridine (DHP) receptors, causing them to change conformation.

This conformational change of the DHP receptors induces the opening of Ryanodine receptor channels (RyR) on the SR. There is thus an increase in permeability to calcium ions on the SR and calcium ions flood into the sarcoplasm.

(remember: sarcoplasm means cytoplasm of muscle cells).

Question 9

Describe the step-by-step process of crossbridge formation in skeletal muscle.

Answer 9

1. In a resting sarcomere myosin hydrolyzes ATP to ADP + P.
2. Calcium binds to troponin, pulling tropomyosin out of the way.
3. Attachment of myosin to actin to form cross bridges.
4. Powerstroke as the myosin head pivots, releasing ADP and P.
5. New ATP arrives, detaching myosin from actin.
6. Repeat of ATP hydrolysis, myosin prepares to re-attach to actin.

Question 10

What is the role of ATP in crossbridge formation?

Answer 10

Upon stimulation by action potential and subsequent release of calcium ions, hydrolysis of ATP (forming ADP + Pi) is the first step in the contraction cycle. Later, myosin-actin crossbridges form due to a conformational change amongst the thin filaments (an effect also brought about by calcium presence).

This ATP charged myosin is then able to use its energy to perform a ‘power stroke’, swivelling its globular head toward the centre of the sarcromere. This pulls the thin filament over the thick (which remains stationary), toward the centre of the sarcromere. ADP + Pi are subsequently released.

The myosin head remains attached to the thin filament (crossbridge pertains) until another ATP molecule arrives and occupies the myosin head complex.

Question 11

What physiological event causes skeletal muscle to relax?

Answer 11

1. Sarcoplasmic Ca-ATPase pumps calcium back into the SR.
2. Decrease in free cytosolic calcium concentration causes calcium to unbind from troponin.
3. Troponin permits tropomyosin to return to its blocking position.
4. Myosin-actin crossbridges break.
5. ATP-myosin complex is reformed in heads of thick filaments.

Question 12

Why is maximum force related to the resting length of the muscle myofilaments?

Answer 12

Because it is the arrangement of thick and thin filaments which permits the contraction of the sarcomere, and thus shortening of muscle belly.

Maximal contraction will be achieved when a muscle is at its resting length. Because it is at this length that there is maximum contact between thick and thin filaments, and thus maximal formation of myosin-actin crossbridges. This means the greatest number of power strokes can occur at a singular point in time, and thus, the maximum force of the muscle.

It is also important to note that it is at resting length that filaments are in max contact, however thin filaments are furthest from centre of the sarcomere (M line). This ensures the maximal ability of the sarcomere to shorten (otherwise there would be less space to do so; H zone would have already closed).

Question 13

How does smooth muscle contract given that there is very little troponin in this tissue?

Answer 13

• For the lacking ammounts of troponin within the thin filament of smooth muscle, there are high concentrations of calmodulin (specific calcium binding proteins).
• In smooth muscle myosin ATPase activity is low and actin and myosin are inactive in the presence of ATP so instead a calcium dependant enzyme known as MLCK (Myosin light chain kinase) catylyzes the reaction instead.
• So, upon stimulation calcium levels inside the smooth muscle cell increase and bind to calmodulin which will in turn bind to MLCK. ATP phosphorylation of myosin brings about actin and myosin interaction. Thus increasing muscle tension.