Block IV: SM fibers, NMJ, muscle spindle & golgi tendon

Question 1

What are the skeletal muscle fiber types?

Answer 1

FAST GLYCOLYTIC FIBERS – Type IIb (Fast White Fibers)
FAST OXIDATIVE GLYCOLYTIC FIBERS – Type IIa (Intermediate fibers)
SLOW OXIDATIVE FIBERS – Type I (Slow Red Fibers)

Question 2

Describe the fast glycolytic fobers

Answer 2

-largest in size; stain for fast myosin isozyme and can contract rapidly, but are easily fatigued because they have the smallest
number of mitochondria; and use the less anaerobic glycolysis to generate ATP. Are the fasttwitch fatigue-prone motor units. (In humans now Type IIX or 2X)

Question 3

Describe fast oxidative glycolytic fibers

Answer 3

Intermediate in diameter; stain for fast myosin isozyme and also
allow fast contraction, less easily fatigued than white fibers because they have an intermediate number of mitochondria; and use the more efficient aerobic oxidative phosphorylation to generate ATP. Fast twitch fatigue resistant motor units

Question 4

Describe the slow oxidative fibers

Answer 4

Smallest in diameter; stain for slow myosin isozyme and contract more slowly, least fatiguable of fibers because they have the greatest number of mitochondria and also use the more efficient aerobic oxidative phosphorylation to generate ATP. Slow twitch fatigue-resistant motor units.

Question 5

identify

Answer 5

Stained for mitochondrial NADH; Cross-section of skeletal muscle fibers stained with NADH-TR reaction to show oxidative
enzyme activity(mitochondrial activity). This
Demonstrates both the darker Type I slow oxidative
Fibers and the lighter staining Type II fast glycolytic
fibers

Question 6

What do differences in muscle type correlate to?

Answer 6

Differences in muscle fiber type correlate with function of the muscle. Most mammalian skeletal muscles are a mixture of the
different fiber types thus fine tuning speed & endurance of
muscle.

Question 7

How is the force generated for muscles of the same fiber type?

Answer 7

the force generated is proportional to the crosssectional area of the muscle.

Larger cross-sectional area = greater force.

Both type I and type II fibers are larger in men than in women

Question 8

What innervates fast glycolytic fibers?

Answer 8

(Type IIX are innervated by larger diameter motor neuron axons with a higher rate of repetitive fire, compared to those of slow oxidative fibers.

Question 9

Fiber type is determined by?

Answer 9

motor axon type

Question 10

identify

Answer 10

Fast Glycolytic Fiber (Type IIb – Type IIX in humans (Fast twitch contraction, fewer mitochondria, uses glycolysis, most easily fatigued)

Fast Oxidative Glycolytic Fibers (Type IIa) (Fast twitch contraction also, but intermediate number of mitochondria, uses oxidative
phosphorylation, intermediate level of fatiguability)

Slow Red Fibers (Type I) (Slow twitch contraction rate, large numbers of mitochondria, uses oxidative phosphorylation, is least
fatiguable of fiber types)

Question 11

What is Sarcopenia?

Answer 11

With increasing age, skeletal muscle undergoes this process. Sarcopenia is associated with a loss in skeletal muscle mass, muscle strength and force, and power (force x velocity).

Question 12

Explain ehat happens during sarcopenia

Answer 12

1. Reduction of muscle fiber number is primarily observed with a 30 – 40% decrease in muscle fiber number by the 8th decade. This loss is greater in men particularly in the lower limb muscles. Women tend to lose more muscle mass in the arms
2. The loss of fibers is greatest for type II fibers (Type IIa and Type IIx) as compared to type I fibers, and there is a 10– 40% reduction in fiber size for the type II
3. The reduction in fiber number correlates with a reduction in the number of satellite cells associated with the type II fibers, and a reduction in satellite cell activation that occurs due to muscle
   damage and muscle repair in response to interleukin-6 (IL-6)

Question 13

What is the Neuromuscular junction?

Answer 13

Site of innervation of skeletal muscle fibers by motor neurons. Free nerve endings lie in depressions on skeletal muscle surface known as motor end plates

Question 14

What are the junctional folds?

Answer 14

The skeletal muscle cell surface is highly folded to form junctional folds which increase surface area for the binding of the acetylcholine released by the axonal terminal to the nicotinic acetylcholine receptors in the sarcolemma

Question 15

identify

Answer 15

longitudinal section of skeletal muscle
showing the sarcomeric striations

Question 16

identify

Answer 16

Micrograph stained to show neuromuscular junction on skeletal muscle fibers

Question 17

identify

Answer 17

EM of a neuromuscular junction showing the Scwann cell (S)
axon, and skeletal muscle surface with synapic clefts (SnC) and junctional folds.

Question 18

Explain the events at the NMJ

Answer 18

1. Upon firing of the motor neuron, acetylcholine within synaptic vesicles in the axonal terminal is released by exocytosis of the vesicle content into the synaptic cleft and binds to a nicotinic acetycholine receptor(ACh receptor)) in sarcolemma of skeletal muscle cell.
2. This causes depolarization of muscle plasma membrane by
   opening of Na+ channels.
3. Acetylcholine then broken down by cholinesterase in basal lamina and cycle repeats

Question 19

What are some auto-immune factors acting at NMJ?

Answer 19

Myasthenia gravis - auto-immune antibodies block, alter or destroy the acetylcholine receptors thus blocking stimulation of the skeletal muscle

Lambert-Eaton myasthenic syndrome (LEMS) - Associated with small cell carcinoma of the lung involves antibodies against many of the presynaptic membrane proteins

Question 20

What are some toxins and venoms that act at NMJ?

Answer 20

Botulinum toxin from Clostridium botulinum
Tetanus toxin from Clostridium tetani
Black widow spider toxin
Snake toxins – Some snake venoms, for example beta-bungarotoxin, block
release of the synaptic vesicles at the presynaptic terminal

Question 21

How does ALS Lou Gehrig’s disease correlate to NMJ?

Answer 21

Not directly but neurons die. Amyotrophic Lateral Sclerosis (ALS – Lou Gehrig’s Disease) – Due to a progressive death of neurons in the spinal cord and brain that innervate the voluntary muscles. No cure.

Question 22

What are symptoms of Myasthenia Gravis?

Answer 22

1. Weakness and rapid fatigue of any of the voluntary muscles when exercised – for example the leg, arm, and neck muscles
2. Drooping of one or both eyelids (ptosis)
3. Double vision (diplopia), which may be horizontal or vertical, and improves or resolves when one eye is closed
4. Impaired speaking, swallowing, and chewing

Question 23

Myasthenia gravis results from?

Answer 23

Typically results from binding of autoimmune antibodies to the nicotinic acetylcholine receptors at the neuromuscular junction. These blocked receptors will be internalized by endocytosis causing a net depletion of the receptors over time with greatly impaired voluntary muscle contraction.

Less commonly can also result from antibodies to muscle-specific receptor tyrosine kinase or against another protein, called lipoprotein-related protein 4

Question 24

Explain the Botulinum & tetanus effects at synapse

Answer 24

1. The botulinum toxin from Clostridium botulinum is endocytosed into the neuronal terminal. Acidification of the endocytosed vesicle results in the translocation of the toxin into the cytoplasm where it cleaves synaptobrevin (VAMP) a V-SNARE protein and the T-SNARE proteins Syntaxin and SNAP-25
2. This blocks the fusion of the synaptic vesicle with the pre terminal synaptic membrane thus blocking transmission at the neuronal synapse
3. Tetanus toxin from Clostridium tetani is similar, but is transported to the spinal cord where it translocates to the presynaptic terminal of inhibitory neurons where it blocks their inhibition of the large motor neurons leading to sustained
   contraction of muscles

Question 25

What is the muscle spindle and golgi tendon organ?

Answer 25

Stretch receptors in the skeletal muscle and in the
tendon

Question 26

By what is the muscle spindle surrounded?

Answer 26

Surrounded by both external and internal CT capsules and are spindle-shaped like elongated footballs

Question 27

WHat are the intrafusal fibers and the types?

Answer 27

Muscle spinde is Characterized by the presence of 3 -12
specialized muscle fibers called intrafusal fibers that act as sensory
detectors of stretch in the skeletal muscles.

Intrafusal fibers are smaller in diameter than the unmodified fibers. 2 types = nuclear bag fiber & nuclear chain fiber

Question 28

What fibers surround normal skeletal muscle fibers?

Answer 28

extrafusal

Question 29

identify

Answer 29

Micrograph of labeled muscle
spindle with intrafusal and extrafusal fibers

Question 30

Explain the function of the muscle spindle

Answer 30

FOR RPEVENTION OF OVERSTRETCHING
1. Branches of a large sensory nerve fiber (type 1a)wrap around each intrafusal fiber at the nuclear level and respond to the stretching of the fibers by initiating action potentials, the rate of which corresponds to the degree of stretching.

2. The activation of these sensory nerves is carried to the spinal cord as part of a reflex arc which then causes activation of alpha-motor neurons whose axons innervate the extrafusal fibers of the same muscle. Contraction of the extrafusal fibers acts to reduce the stretching of the muscle.
3. In addition, gamma-motor neurons can innervate the intrafusal fibers to produce a controlled contraction of the fibers (priming) which can increase their sensitivity to additional stretch.

Question 31

What is the golgi tendon organ?

Answer 31

A similar sensory organ is found in the tendon typically near the juncture of the muscle and tendon.

It is associated with branches of a sensory nerve type 1b, and
serves a similar sensory function but at the level of monitoring stretch directly in the tendon not the muscle.

Question 32

mention some muscle pathologies

Answer 32

Compartment syndrome- is a painful condition, with muscle pressure reaching dangerous levels. Acute compartment syndrome is a medical emergency, usually caused by trauma, like a car accident or broken bone. Chronic (or exertional) compartment syndrome is caused by intense, repetitive exercise and usually stops with rest or changes in routine.

Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of the muscle breakdown products, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure.

Polymyositis (PM) is a type of chronic inflammation of the muscles (inflammatory myopathy). The inflammation of polymyositis is mainly found in the endomysial layer skeletal muscle, whereas dermatomyositis (which can also affect muscles) is characterized primarily by inflammation of the perimysial layer of skeletal muscles.

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. In the case of skeletal muscle they usually present as: muscle weakness, exercise intolerance, cramps, excretion of muscle protein myoglobin in urine (myoglobinuria) On
biopsy, the muscle tissue of patients with these diseases usually demonstrate “ragged red” muscle fibers with increased reactivity for succinate dehydrogenase and a decreased
reactivity for cytochrome c oxidase.