Nerve, muscle, and NMJ

Question 1

Normal skeletal muscle

Answer 1

Has a monotonous appearance.
Polygonal shape
Peripheral nuclei
No connective tissue or cells between fibers
Minimal variation in fiber size

Question 2

Normal nerve

Answer 2

When stained with Toluidine blue to highlight myelin.
– The central clearing is the axon.
– There is a mixture of thick and thinly myelinated axons as well as unmyelinated axons

Question 3

Trichrome stain for muscle

Answer 3

Can show connective tissue and precipitated mitochondria will appear red.

Question 4

NADH stain for muscle

Answer 4

To assess oxidative enzyme function in muscle

Question 5

The ATPase stain for muscle

Answer 5

Highlights different fiber types.
– Type 1 fibers are rich in oxidative enzymes, mitochondria, and lipid allowing for protracted slow action.
– Type 2 fibers are rich in glycogen and glycolytic enzymes. They are capable of fast, powerful, tonic contraction
– These fibers are present in all muscles and should be intermixed like a checkerboard.

Question 6

Dystrophin stain for muscle

Answer 6

Many but not all of the genetic causes of muscular dystrophy localize to proteins in the muscle membrane. Thesevproteinsvcanvbe stained used immunochemistry.
– Normal muscle will have staining of the muscle membrane.

Question 7

Ia/Ib sensory fibers

Answer 7

A-alpha
Myelinated
Diameter: 13-20 μm (Large)
Speed: 50-75 m/sec, perhaps up to 80-120 m/sec (Fastest)
Ia to muscle spindle afferents, DTR; Ib to golgi tendon organs

Question 8

II sensory fibers

Answer 8

A-beta
Myelinated
Diameter: 6-12 μm (Medium)
Speed: 35-70 m/sec (Fast)
Pacinian & Meissner’s corpuscles, light touch, precise touch, vibration, cutaneous mechanoreceptor

Question 9

III sensory fibers

Answer 9

A-delta 
Myelinated
Diameter: 1-5 μm (Small)
Speed: ~20 m/sec, range 3- 30m/sec (medium)
Fast precise pain

Question 10

C-fibers

Answer 10

Unmyelinated
Diameter: 0.2-2.0 μm
Speed: 0.5-2 m/sec (slowest)
Pain, itch

Question 11

Alpha motor neurons

Answer 11

Fastest (50-75 m/sec, perhaps up to 80-120 m/sec); 13-20 μm

Movement of skeletal muscle (“extrafusal fibers”)

Question 12

Gamma motor neurons

Answer 12

Medium speed (most sources say 20-40 m/sec in humans); 5-8 μm
Keeping muscle spindle apparatus under proper tension (fire constantly, “intrafusal fibers”)

Question 13

Pain sensation

Answer 13

Small myelinated A-delta nociceptors (20 m/s)
Unmyelinated C-fiber nociceptors (~1-2 m/s)
Respond to excessive pressure, inflammatory mediators, tissue damage, acidosis, etc.

Question 14

Cold sensation

Answer 14

Small myelinated fibers (A-delta fibers) and possibly by unmyelinated afferents

Question 15

Warm / Heat sensation

Answer 15

Unmyelinated, warm-specific C-fibers

Express ion channels activated by heat

Question 16

Menthol and cold

Answer 16

Cold sensitive C-fibers express TRMP8
– TRMP8 “the menthol receptor” is activated by cold (<15 C) and/or menthol
– Explains intense cold sensation of drinking ice water with a menthol mint

Question 17

Capsacin and heat

Answer 17

Warm / Heat sensitive neurons
– Express ion channels activated by heat (several types, including TRPV1)
– TRPV1 “vanilloid receptor” is activated by heat and/or capsaicin
– Capsaicin is the active ingredient in hot peppers
– Capsaicin cream therapeutic Mechanism: chronic use depletes neurons of Substance P

Question 18

C-fiber afferents

Answer 18

Question 19

A-delta nociceptor afferents

Answer 19

Question 20

Pacinian corpuscles:

Answer 20

Specialization in dermis, often near joints
Vibration, joint motion, rapid extinction
Type II afferents (faster than A-deltas, slower than type I afferent)

Question 21

Meissner’s corpuscles

Answer 21

Skin (concentration in finger tips, lips, etc.)
Light touch, vibration
Type II afferents (faster than A-deltas, slower than type I afferents)

Question 22

Golgi tendon organs

Answer 22

Locatedintendons,sensetension, 1B afferents

Protection from excessive contraction

Question 23

Muscle spindle afferents

Answer 23

Special“intrafusal” muscle fibers sense changes in muscle stretch
• Ia myelinated afferents (fastest) and IIa afferents
• Efferent innervation (gamma motor neurons), constantly active, keeps fiber taught to detect sudden movements **

Question 24

Epimysium, perimysium, and. endomysium

Answer 24

– Epimysium: thicker layer surrounding all fascicles. Dense connective tissue.
– Perimysium: the thin layer surrounding each group of muscle cells forming a fascicle
– Endomysium: thin layer surrounding an individual muscle fiber.

Question 25

Thick filament muscle

Answer 25

Myosin

Question 26

Thin filament muscle

Answer 26

Actin
Troponin
Tropomyosin

Question 27

Sacromere unit

Answer 27

– The thin filaments extend from the Z line.
– The I band is an area with only thin filaments.
– The H zone is an area with only thick filaments.
– The A band is the entire length of thick filaments including the H zone and areas where the thick and thin filaments interact

Question 28

Energy supply for muscle

Answer 28

Question 29

Energy source for muscles at rest and low intensity exercise

Answer 29

At rest, muscles use fatty acids and thus beta- oxidation of fatty acids
At low intensity exercise (defined by maximal oxygen uptake < 50%), muscles use blood glucose and free fatty acids.
After a few hours of low intensity exercise, fatty acids are the primary source of energy.

Question 30

Energy source at high intensity exercise for muscle

Answer 30

High Intensity Exercise
• Glycogen is the major energy source for high intensity exercise (defined by maximal oxygen uptake > 50%).
– If the maximal oxygen uptake < 80%, then glycogen is metabolized aerobically (glycolosis, citric acid cycle, and oxidative phosphorylation)
– If the maximal oxygen uptake is >80%, then glycogen is metabolized anaerobically (glycolosis alone).

Question 31

NMJ transmission - vesicle fusion

Answer 31

Question 32

Neuron depolarization

Answer 32

Question 33

Neuron depolarization

Answer 33

Question 34

Diffusion and recycling of acetylcholine

Answer 34

Question 35

Safety factor at the NMJ

Answer 35

Reliable transmission of activity from nerve to muscle is necessary for the normal function of the body. The term ‘safety factor’ refers to the ability of neuromuscular transmission to remain effective under various physiological conditions and stresses. This is a result of the amount of transmitter released per nerve impulse being greater than that required to trigger an action potential in the muscle fibre. The safety factor is a measure of this excess of released transmitter.

Answer 36

Step 1 in muscle contraction: Acetylcholine binding to the Acetylcholine receptor
Step 2 in muscle contraction: Opening of voltage-gated sodium channels (SCN4A)
Step 3 in muscle contraction: Calcium influx
- Depolarization of the muscle cell membrane causes a conformational change in the voltage- sensitive dihydropyridine receptor (DHPR)
- This in turn causes opening of the ryanodine receptor calcium channel located on the sarcoplasmic reticulum
Step 4 in muscle contraction: Calcium diffuses along thick and thin filaments where it binds troponin on the thin filaments, exposing myosin binding sites on actin, on the thin filaments
Step 5 in muscle contraction: Myosin and actin interaction (see image)
Step 6 in muscle contraction: Termination of muscle contraction: Calcium removal by a Ca2+ ATPase (SERCA)