Lecture 7: Skeletal Muscle

Question 1

Characteristics of skeletal muscle cells

Answer 1

AKA striated muscle fiber. Very large, elongated, and multinucleated. Fuse from undifferentiated myoblasts.

Question 2

Satellite cells

Answer 2

Quiescent skeletal muscle stem cells. Proliferate in response to strain/injury and mediate hypertrophy of other fibers in repair.

Question 3

Skeletal muscle striations

Answer 3

Composed of cytosolic thick myosin and thin actin filaments.

Question 4

Myofibril

Answer 4

Thick/thin filament bundles that attach to tendons and extend end to end within muscle cells, filling most of the cytoplasm

Question 5

Thick filaments

Answer 5

Primarily made of myosin. Tails extend along axis of thick filament with heads extending out the sides as cross bridges

Question 6

Thin filaments

Answer 6

Primarily made of actin in 2 helical intertwined chains; also nebulin, troponin, and tropomyosin. Each actin molecule is a myosin binding site

Question 7

Myosin structure

Answer 7

Composed of 2 heavy chains and 4 light chains. Heavy chains intertwine into a long tail and form the two globular heads of the motor region. Light chains are at the neck.

Question 8

Myosin motor head region

Answer 8

Responsible for contacting the thin filament and exerting force. Contains one binding site for actin (thin-f) and another for ATP (myosin-ATPase)

Question 9

Sarcomere

Answer 9

Basic contractile unit. Bounded by Z-lines and composed of overlapping thick + thin filaments and titin

Question 10

Sections of sarcomere

Answer 10

Z-line, M-line, I band, A band, H zone

Question 11

Z-line (disc)

Answer 11

Defines boundary of sarcomere and anchors thin filaments + titin

Question 12

M-line (disc)

Answer 12

Line (disc) in middle of sarcomere that binds thick filaments + titin

Question 13

I band

Answer 13

Area of sarcomere that contains only thin filaments, no thick

Question 14

H zone

Answer 14

Area of sarcomere that contains only thick filaments, no thin

Question 15

A band

Answer 15

Anisotropic band. Area of sarcomere with entire thick filament. Contains overlapping thick + thin filaments

Question 16

Titin

Answer 16

Protein that gives sarcomere its elastic properties. Links to M-lines and thin filaments.

Question 17

Transverse arrangement of thick and thin filaments

Answer 17

Each thick filament is surrounded by a hexagon of thin filaments; each thin-f is surrounded by a triangle of thick-f. Thus there are about 2x as many thin as there are thick filaments.

Question 18

Sarcoplasmic reticulum

Answer 18

Network of tubules/sacs that form sleeves around each myofibril and are responsible for storing/releasing Ca2+

Question 19

Terminal cisternae

Answer 19

Located at ends of sarcoplasmic reticulum. Store a high concentration of Ca2+ through calsequestrin and are connected by tubes.

Question 20

Transverse tubules

Answer 20

Invaginations continuous with the sarcolemma and whose lumen is continuous with the ECF. Allow APs to penetrate into the muscle fiber.

Question 21

Contraction vs relaxation

Answer 21

Activation of force generating cross-bridges in muscle. Relaxation is inactivation

Question 22

Alpha motor neuron properties

Answer 22

Alpha motor neurons innervate skeletal muscle fibers and are myelinated + large diameter. 1 motor neuron axon branch innervates 1 fiber, so 1 motor neuron innervates many fibers.

Question 23

Motor unit

Answer 23

Comprised of a motor neuron and all its innervated fibers. All fibers within a motor unit get stimulated together.

Question 24

Motor end plate

Answer 24

Sarcolemma under the motor axon terminal with junctional folds for more surface area. Contains ACh receptors.

Question 25

Neuromuscular junction

Answer 25

Structure composed of the motor axon terminal and the motor end plate

Question 26

Motor neuron action potentials per muscle fiber action potentials

Answer 26

The NMJ has 1:1 transmission (1 neuron AP means 1 muscle fiber AP)

Question 27

Acetylcholinesterase

Answer 27

Enzyme that breaks down ACh at the NMJ for reuptake and recycling.

Question 28

How does curare affect muscle contraction?

Answer 28

Inverse agonist for nicotinic ACh receptors. Binds with high affinity without opening channels while resisting AChesterase breakdown, preventing fiber activation.

Question 29

Tropomyosin

Answer 29

Protein chains 7 g-actin long that run along the thin-f and partially cover actin's myosin-binding site, preventing cross-bridge contact at rest

Question 30

Troponin

Answer 30

"Staples" tropomyosin to its blocking position on actin, 1 per tropomyosin. Complex of TnI, TnT, TnC.

Question 31

TnI

Answer 31

Inhibitory subunit of troponin. Binds complex + tropomyosin to actin filament

Question 32

TnT

Answer 32

Tropomyosin-binding subunit of troponin

Question 33

TnC

Answer 33

Calcium-binding subunit of troponin

Question 34

Excitation-contraction coupling

Answer 34

Sequence by which an AP in the sarcolemma activates force-generating mechanism

Question 35

How do organophosphates affect skeletal muscle?

Answer 35

Organophosphates inhibit AChesterase, preventing repolarization for further APs. Can be rescued with pralidoxime

Question 36

What are rocuronium and vecuronium used for and why?

Answer 36

Both are used in anesthesia. They are nondepolarizing long-lasting NMJ blocks that act similar to curare

Question 37

How does botulinum toxin affect the NMJ?

Answer 37

Botunlinum cleaves SNARE proteins, preventing vesicle fusion and thus NT release.

Question 38

Dihydropyridine receptor (DHPR)

Answer 38

The DHPR is a transmembrane voltage-sensitive Ca2+ channel in the t-tubule that acts as a voltage sensor for the muscle fiber

Question 39

Ryanodine receptor (RyR)

Answer 39

Sarcoplasmic reticulum transmembrane calcium channel which is connected to the DHPR by a foot process, allowing the DHPR to open the RyR and briefly release calcium from the SR on stimulation.

Question 40

How much calcium is released from 1 skeletal muscle AP relative to the muscle fiber?

Answer 40

1 AP typically releases enough calcium to briefly saturate all troponin binding sites

Question 41

Sliding filament mechanism

Answer 41

Contraction happens by sliding thick and thin filaments past each other, shortening sarcomeres without changing filament length

Question 42

Cross-bridge cycle (Lymn Taylor Model)

Answer 42

1. Actin binding (tropomyosin moves) 2. Power stroke (ADP leaves) 3. Dissociation from actin (ATP binding) 4. Myosin cocking (ATP hydrolysis)

Question 43

Roles of ATP in skeletal muscle contraction

Answer 43

1. Maintain membrane excitability through resting potential 2. Regulate cytosolic Ca++ 3. Provide energy for cross-bridge motion 4. Dissociate myosin from actin

Question 44

Rigor mortis

Answer 44

Without fresh ATP calcium leaks out of the SR -> cross-bridges power stroke but can't release actin -> muscle rigidity

Question 45

Rate limiting step of myosin ATPase

Answer 45

Myosin ATPase is rate limited by product dissociation (releasing ADP + Pi); bound actin increases this step by over 2000X

Question 46

SERCA

Answer 46

Sarcoendoplasmic Reticulum Calcium ATPase: removes cytosol Ca++ and pumps back into SR; works much slower vs action potential time, so 1 AP lasts 1-2 ms but the corresponding contraction lasts ~100 ms.