7. Physiology of Skeletal Muscle Adaptation/Repair, Muscle Disorders Flashcards
Muscle Fatigue
• Due to prolonged heavy work: above \_\_\_\_ of maximal aerobic capacity. • Decreased capacity of muscular work and reduced efficiency of performance. – Lower \_\_\_\_. – Longer \_\_\_\_ time. – Requires a period of \_\_\_\_. • Types: – Psychological: • Depends on \_\_\_\_ of the individual. – Muscular: • Results from \_\_\_\_ depletion. – Synaptic: • Depletion of \_\_\_\_ in the neuromuscular junction.
70%
velocity and force of contraction
relaxation
rest
emotional state
ATP
acetylcholine
Muscle Fatigue Mechanisms
• High-frequency stimulation fatigue:
– Induced by stimulation at a rate ____ than necessary for a ____.
– Failure in the conduction of action potentials in ____.
– ____ recovery: tens of seconds.
– Rarely (if ever) happens in vivo: ____ mechanisms.
• Low-frequency stimulation fatigue:
– Induced by prolonged or repeated ____.
– Due to metabolism:
• Depletion of energy stores (ATP) and buildup of ____.
• Reduction in Ca2+ trafficking from the SR: lower ____, increased ____
time.
– Longer ____.
higher fused tetanus T tubules rapid neural safety
tetanic stimulation crossbridge metabolites peak force relaxation recovery
Adaptation and Myoplasticity
• ____: Ability of skeletal muscle to remodel.
• Quantity: e.g. ____ (enlargement) of the muscle organ.
• Quality: e.g. switch in Myosin Heavy Chain ____ (from Fast IIb to Fast IIa),
____ (from glycolysis to oxidative phosphorylation).
• Adaptation: • More effective \_\_\_\_ exercise. • Depends on type of \_\_\_\_ (training): resistance, plyometric (max. force, short intervals), endurance. • Easily reversible when stimulus is diminished or removed (inactivity): \_\_\_\_. • Muscle adapts in different ways: • \_\_\_\_ adaptation. • \_\_\_\_ adaptation. • \_\_\_\_ adaptation.
myoplasticity
hypertrophy
gene expression
metabolism
aerobic or resistance
exercise
atrophy
metabolic
cellular
neural
Metabolic Adaptations
• Heavy work, untrained muscle: • Low O2 availability: \_\_\_\_. • Accumulation of pyruvate: negative feedback on glycolysis. • Adaptation: • Reduction of pyruvate to \_\_\_\_: allows glycolysis to continue. • Regeneration of \_\_\_\_. • Production of lactate → \_\_\_\_
If forcing an untrained muscle to take heavy work > training provides additional vascularization; in an untrained muscle there is low ____, therefore the availability of oxygen is low > obligated to use ____ as a source of energy
Accumulation of pyruvate, acts on a feedback mechanism and stops the pathway (glycolysis can only be maintained for a ____ time)
Lactate is an acid, and must be eliminated, but it doesn’t happen rapidly; it will be regenerated back to pyruvate but it will occur in the liver later
Generation of lactate is evidence of ____ or muscle “shortness?”, and the oxygen-deficit phenomena
glycolysis
lactate
NAD+
oxygen deficit phenomenon
vascularization
glycolysis
limited
heavy work
Metabolic Adaptations: Oxygen Deficit
- Difference between oxygen uptake of the body during ____ of exercise and during a similar duration in a ____ of exercise.
- Allows short-term ____ metabolism.
- Must be re-payed:
- During ____ in the TCA cycle.
- During regeneration of ____ stores from oxidative phosphorylation ATP.
• Recovery phase after heavy exercise: O2 consumption and lung ventilation rates remain
elevated.
Why muscles working anaerobically create an overall oxygen-deficit for the body and muscles themselves:
Lactate must be oxidized in the liver (uses energy and oxygen)
After contraction, stores of ATP and creatine phosphate are low > mitochondria regenerated the stores by using ATP that was created during ox phos after the exercise
After heavy exercise, the rates of oxygen consumption are still ____, compared to the body at rest
The oxygen deficit is not as acute, the consumption is not just related to the single exercise
early stages steady state anaerobic lactic acid oxidation creatine-P
very high
Metabolic Adaptations: Myoglobin Content
Similar ____, different ____.
The quaternary structure of hemoglobin confers ____.
tertiary structure
quaternary structure
allosteric properties
Myoglobin avidly binds oxygen
- Mb facilitates diffusion of O2 in exercising muscles.
- Mb most abundant in muscles adapted for aerobic exercise: ____.
Muscles that are rich in ox phos > ____ (slower, but efficient) > contain myoglobin
Myoglobin has oxygen bound to molecule when the pressure of oxygen is ____ > a very good mechanism to store oxygen inside the cells themselves
Only when intracell concentration of oxygen is ____ > myoglobin release oxygen atoms that can be used in ox phos; also provides a very ____ of oxygen to those muscles
red/dark fibers
red fibers
very low
low
Cellular Adaptations
• Changes in skeletal muscle configuration and structure:
– ____ activation.
– ____ to existing fibers.
• Occurs with ____ and ____.
• Hypertrophy vs hyperplasia:
– ____: muscle fibers growing in size → increase in cross-sectional area.
– ____: muscle fibers growing in number (more common in ____).
Activation of ____ produces a bigger, thicker fiber > increase in cross-sectional area (hypertrophy) (skeletal muscle cell is a ____ cell, fused, contain many nuclei) > exert more force; result of resistance training and overloading our muscles
Can also see presence of hyperplasia, increase in actual number of muscle fibers
satellite cell fusion resistance training overloading hypertrophy hyperplasia development
satellite cells
sintitial
Mechanical Properties in Muscle Hypertrophy
• Hypertrophy:
– Increase in cross-sectional area (CSA). – Increase in ____.
• Force-velocity relationships:
– Increase in maximum load (____ > ____).
– No change in ____, but…
– a stronger (“trained”) muscle moves an isotonic load (X) at a greater ____
• Enhanced ____ output.
cross-sectional area (CSA) P0t, P0ut maximum no-load velocity (V0) velocity (Vt > Vut) power
Neural Adaptations
• Recall the muscle physiology lecture:
• Motor unit: Neuron + innervated muscle fibers.
• ____: Increasing force via recruitment of additional
motor units.
• ____: Increasing force via greater neural discharge
frequency.
• Maximum muscle force then requires:
• Activation of all ____.
• Maximal ____.
number coding
rate coding
motor units
rate coding
Neural Adaptations
• Neural adaptation: • Increased \_\_\_\_ recruitment. • Decreased \_\_\_\_ of motor unit recruitment. • Decreased \_\_\_\_ recruitment. • Increased neural coordination • Increased activation of \_\_\_\_ motor units.
• Timeline of muscle adaptation: • Early changes: \_\_\_\_ adaptation. • Later changes: \_\_\_\_ (increasing CSA). • Years: \_\_\_\_, no gains from training (anabolic steroids!).
MU
neural inhibition
antagonist
agonist
neural
hypertrophy
plateau
Neural Adaptations
Training the muscles, you change both the ____
Compare increase in force during long term training with the types of adaptation that take place; most training studies: most adaptation that takes place is ____ (by reorganizing and remodeling the coordination and neural control); if training increase, neural stimulation hits a plateau but ____ is still increasing, but now a recruitment of satellite cells is now taking place, but eventually the muscle strength is maximized
Only way to increase force afterwards is to take substances that increase the hypertrophy beyond what is normal
spatial and temporal summation
neural
force
Muscle De-training and Atrophy
- ____:
- Mild decrease in skeletal muscle functionality due to lack of exercise.
- Atrophy: ____ in muscle function.
- Occurs with immobilization, ____ rest, aging, ____ flight.
- ____ decrease in muscle mass and fiber diameter.
- Large reduction in ____ and/or load.
- Significant reduction in metabolic and exercise capacity in ____ weeks.
- Complete loss of training adaptations in a few ____.
de-training
severe bed space 30-50% recruitment frequency 1-2 months
Mechanisms Associated with Muscle Growth and Atrophy
Going from untrained muscle to trained muscle > activation of ____ and high levels of ____
Atrophy state > high rates of ____ and ____ (decrease in diameter of muscle)
satellite cells
protein synthesis
protein degradation
apoptosis
- Muscle Damage and Repair: Stages of Muscle Damage
Begin with normal muscle and induce with ____ contractions (good at creating damage) > numerous effects > used to study the damage the muscles show following use
1.– During exercise: Mechanical (strain) damage: • Myofibril damage: – Disrupted sarcomeres → Effect on \_\_\_\_ → Lower force. • Sarcolemma damage. – \_\_\_\_ dysfunction (reversible) → Lower force. • SR damage. – Ca2+ influx. » Protease activation – damage to \_\_\_\_. » Phospholipase activation – damage to \_\_\_\_.
- After exercise: ____ response.
If fiber dies, there is an ____ decrease in force
Swelling and soreness is due to a ____ due to a fact that cells are dying and leaking their contents outside
eccentric optimal length excitation/coupling cytoskeleton sarcolemma inflammatory irreversible inflammatory process
- Muscle Damage and Repair: Eccentric vs Concentric Contractions
Concentric contraction = contraction while ____
Eccentric contraction = contraction while ____
shortening
lengthening
- Muscle Damage and Repair: Sarcomere Damage
• Damage occurs during ____ (eccentric) movements.
• Extent of injury more related to ____ than force or velocity.
• ____ fibers become overstretched, which become damaged.
• Damage to the Z disk (known as Z-disk streaming):
– Massive loss of Z disk integrity following muscle
injury.
– Z disk structure is disrupted and Z disks are not in ____
with each other (arrowheads).
– Muscle cell separation from the ____ and
____ (asterisks).
• Affects ____ fibers more than ____ fibers.
If Z-disks are compromised > myofilaments have no structure to which they can attach, and they have no structure onto which they can exert a ____
lengthening length weaker line basal lamina endomysium
fast
slow
force
- Muscle Damage and Repair: Myofibril Damage
• Hypertrophy and myofibril proliferation:
– Myofibrils increase in mass and CSA from addition of actin/myosin to ____.
– Myofibrils reach critical mass where forceful actions tear Z disks ____.
– Myofibrils may ____.
When you have too many filaments because the cell has become larger, the angle at which the filaments attach themselves to the Z-disk is not ____; when filaments contract, the forces that act on Z-disks come at an ____ > Z-disk breaches (streaming)
periphery
longitudinally
split
flat
angle
- Muscle Damage and Repair: Sarcolemma Damage
• Damage to the sarcolemma:
– EM photo:
• Muscle of a runner after a ____ race, showing damage to the sarcolemma.
Even ____ muscles can undergo damage like this
marathon
well-trained
- Muscle Damage and Repair: Stages
• Degenerative (____ response) phase (panel B):
– ____ (blue-stained cells: neutrophils and monocytes) and ____ of muscle fibers (arrows).
– Loss of muscle architecture.
• ____ phase (panel C):
– Activation of ____, differentiation, and fusion into ____.
– Regenerating fibers: ____ caliber (still showing ____ nuclei).
acute
inflammatory response
rapid necrosis
regenerative satellite cells myotubes smaller centrally-located
- Muscle Damage and Repair: Molecular Events
A. Damage to the myofiber.
B. Activation of ____: expansion of the
myogenic cell population.
C. Differentiation: myogenic cells differentiate into
____.
D. Myoblasts ____ to the damaged myofiber (myocyte,
muscle cell) for repair; or to ____ for new
myofiber formation.
E. Growth of repaired or new myofiber.
F. A subset of myoblasts reenters the ____ to replenish the satellite cell pool for subsequent muscle repair.
Similar to training, except no ____ and increase in ____ of the muscle fiber
satellite cells myoblasts fuse each other quiescent state
damage
cross-sectional area
- Muscle Damage and Repair: Myostatin
• Myostatin:
– Belongs to the ____ superfamily.
– ____ regulator of muscle growth and
differentiation.
• “Double-muscled cattle”: – 20% more muscle. – Natural mutations in the Myostatin gene. – Muscle \_\_\_\_. – Low \_\_\_\_ (very lean meat).
TGF-beta
negative
hypertrophy and hyperplasia
fat
- Muscle Damage and Repair: Human Myostatin Null Case
- ____ for a loss-of-function mutation in the Myostatin gene:
- Increased muscle bulk and strength.
- ____: Protruding muscles of the patient’s thigh and calf (arrowheads in panel A).
- At 4.5 years of age, able to hold two 3-kg dumbbells in horizontal suspension with his arms extended.
- No major ____, and intellectually ____.
- Panel C, muscle cross-sectional planes of patient and normal infants.
- Pedigree (panel D): Solid symbols indicate family members exceptionally ____.
Pedigree > shows members of his family that were known to be very strong (although never ____ to see if they were mutants for myostatin)
homozygote hyperplasia medical problems normal strong
genetically studied
- Muscle Disorders
• Skeletal muscle disorders:
– Primary muscle disease (usually ____): ____
– Disorders of neuromuscular transmission: e.g. ____.
– ____ and ____ disorders.
genetic muscular dystrophies myasthenia gravis aging metabolic
