Nerve, muscle, and NMJ Flashcards
Normal skeletal muscle
Has a monotonous appearance. Polygonal shape Peripheral nuclei No connective tissue or cells between fibers Minimal variation in fiber size
Normal nerve
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
Trichrome stain for muscle
Can show connective tissue and precipitated mitochondria will appear red.
NADH stain for muscle
To assess oxidative enzyme function in muscle
The ATPase stain for muscle
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.
Dystrophin stain for muscle
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.
Ia/Ib sensory fibers
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
II sensory fibers
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
III sensory fibers
A-delta Myelinated Diameter: 1-5 μm (Small) Speed: ~20 m/sec, range 3- 30m/sec (medium) Fast precise pain
C-fibers
Unmyelinated
Diameter: 0.2-2.0 μm
Speed: 0.5-2 m/sec (slowest)
Pain, itch
Alpha motor neurons
Fastest (50-75 m/sec, perhaps up to 80-120 m/sec); 13-20 μm
Movement of skeletal muscle (“extrafusal fibers”)
Gamma motor neurons
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”)
Pain sensation
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.
Cold sensation
Small myelinated fibers (A-delta fibers) and possibly by unmyelinated afferents
Warm / Heat sensation
Unmyelinated, warm-specific C-fibers
Express ion channels activated by heat
Menthol and cold
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
Capsacin and heat
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
C-fiber afferents
A-delta nociceptor afferents
Pacinian corpuscles:
Specialization in dermis, often near joints
Vibration, joint motion, rapid extinction
Type II afferents (faster than A-deltas, slower than type I afferent)
Meissner’s corpuscles
Skin (concentration in finger tips, lips, etc.)
Light touch, vibration
Type II afferents (faster than A-deltas, slower than type I afferents)
Golgi tendon organs
Locatedintendons,sensetension, 1B afferents
Protection from excessive contraction
Muscle spindle afferents
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 **
Epimysium, perimysium, and. endomysium
– 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.
Thick filament muscle
Myosin
Thin filament muscle
Actin
Troponin
Tropomyosin
Sacromere unit
– 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
Energy supply for muscle
Energy source for muscles at rest and low intensity exercise
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.
Energy source at high intensity exercise for muscle
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).
NMJ transmission - vesicle fusion
Neuron depolarization
Neuron depolarization
Diffusion and recycling of acetylcholine
Safety factor at the NMJ
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.
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)
