Lecture 16 - Mechanisms of skeletal muscle fatigue Flashcards
What is muscle fatigue?
Force loss during a sustained maximum voluntary contraction
loss of maximum or potential performance
need to be careful which aspect of performance is being considered
'’A failure to maintain the required or expected force’’
What is the distinction we need to be clear about when talking about ‘fatigue’
need to be clear about which aspect is under consideration - i.e sensations and perceptions of exhaustion or changes in muscle function
True or False
The extend of fatigue may vary according to the method of testing
true
changes in function may appear greater for _____ contractions than for _____stimulation
changes in function may appear greater for voluntary contractions than for tetanic stimulation
True or False
The fatigue levels may differ if muscle is tested at one frequency of stimulation than another
true
What things does the rate of fatigue depend on?
muscles employed
the relative intensity of the exercise
whether contractions are intermittent or continous
What is the definition of weakness?
an inability to develop an initial force appropriate for the circumstances
e.g elederly person with atrophied muscle unable to get up from a chair
What are the two potential sites of Muscle Fatigue?
Central - Brain and spinal cord; involves motivation and central motor pathways
peripheral - peripheral nerves and muscles involves sites within motor units (i.e motor neurons, peripheral nerves, motor endplates, muscle fibres)
What are the factors of central fatigue?
emotional and psychological factors which infleunce our motivation to perform a task
How does the CNS contribute to muscle fatigue?
reduced supraspinal ‘‘drive’’ of MNs
Impaired SC transmission
neuromuscular transmission failure
recruitment of MUs
reduced motor unit firing frequency
inhibitory input from muscle afferents
What are the two schools of thought regarding the origins of the sense of muscular effort?
A) A sense of muscular effort due to a collateral pathway reaching a conscious centre - ‘‘telling’’ the muscle what to do
B) sense of effort due to afferent information from active (contracting) muscle - comes from what the muscle is doing
How do some experiments argue AGAINST a central mechanism for fatigue?
there is no difference in force output of voluntary contraction vs. force output with electrical stimulation
during voluntary muscle fatigue - imposing electrical stimulation was unable to restore tension (in some studies)
How do some experiments argue FOR a central mechanism for fatigue?
Shout during exertion = increase force
electrical stimulation of fatigued muscle = increase force
contractions of fatigue with eyes closed, simply opening the increases force
alterations in CNS arousal can facilitate MU recruitment
The majority of evidence indicates that central factors play a ___ role in mediating fatigue
lesser
there’s still alot of debate on this
Given central factors may not be the major cause of fatigue, what are the factors that can contribute to peripheral fatigue?
neural
mechanical
biochemical
what are the changes from fresh to fatigued muscle fibres?
Force is decreased
Force is developed more slowly
relaxation is prolonged - thought to be due to a decreased rate of cross-bridge detachment. Also impairment of SR pump functiom such that the reuptake process fails or takes longer
This tells us there are some biochemical changes - intracellular metabolic disturbances
What is Excitation-contraction?
E-c coupling is defined as the events that include depolarisation of the t-system that activates specialised voltage sensors (DHPR), which in turn open ryanodine receptors (RYR, also called Ca release channels) in the adjacent SR membrane, allowing Ca to enter cytoplasm and intiate crossbridge cycling
What are the considerations when looking at the NM junction as a source of peripheral fatigue?
supplies of NT are exhausted?
insufficient ACh to transmit presynaptic AP
below threshold for AP
^ Evidence is mostly against this.
perhaps could occur during prolonged isometric contraction, but NOT during intermittent activation
At change in frequency stimulation to a lower level will result in a rapid increase in force - what does this indicate?
failure of AP
loss of membrane excitability - K+ accumulation in the t-tubules
impairment of the Na/K exchanger mechanisms
Simply by switching the to lower frequency, the exchanger is back in action and we get a restoration of acitivity and hence, force
High frequency fatigue will involve
fast onset
fast recovery - will be able to to produce the same level of force quicky
occurs during exercise that requires intense, near maxial muscle contraction
metabolic fatigue will involve
slower onset
slower recovery
induced by less intense, submaximal contraction
characterised by metabolic stress, including acidosis and phosphocreatine depletion
recovery can be hours-days
What is the most likely cause of high frequency fatigue?
T-tubule conduction failure - we know the force recovers quickly, hints at what mechanism it is
What are the potential biochemical factors to fatigue?
loss of glycogen, ATP (fatigue could be a protective mechanism against total ATP depletion - it is required from cellular homeostasis)
accumulation of lactate and H+
accumulation of Pi
accumulation of ADP
fall in PCr
Intramuscular ATP falls to only __% of pre-exercise levels at fatigue, due CP buffering
60%
If low ATP caused fatigue, resting fatigued muscles would develop…
tension from rigor cross-bridges
The rateof ATP _____, however, is reduced at fatigue
ATP hydrolysis
Why does High-intensity resistance training result in acidosis (the burn)?
The body’s more explosive fast twitch MUs are recruited to overcome the resistance loads
The fuel for is energy demand comes primarily from the anaerobic metabolism
Fast-twitch muscle fibres have fewer mitochondria than slow twitch
Thus, during high-intensity resistance training there is a greater accumulation of protons causing acidosis
How does H+ reduce force?
reducing the sensitivity of the troponin for Ca
slowing glycolysis
interfereing with actin-myosin cross-bridge cycling
while a fall in pH may play some role int he development of fatigue…
it cannot be the only cause
Fatigue is multi-factorial
how does lactate affect fatigue?
lactate is likely not the cause of fatigue Acidity associated with increase lactate accumulation may actually help delay the onset of muscle fatigue
What is the evidence against pH and lactate as influencing fatigue?
McArdle’s disease
deficiency in muscle glycogen phosphorylase
results in muscles that are unable to break down glycogen
no glycolysis, therefore lactate or H+ accumulation, et fatigue is more rapid in McArdle’s patients
Ca2+ is a critical factor in ____
fatigue
Higher Ca2+ concentration results in…
more force
During intense activity and high energy demand, Pi accumulates from..
the splitting of ATP and breakdown of PCr
True or False
accumualtion of Pi reduces muscle fibre force by up to 30%
true
just these kind of metabolites accumualting in a bath drops the levels of force
tells us the myofilaments are highly sensitive to the circulating environemnt
Mg2+ can compete where in the contraction mechanism?
at the binding site of troponin. Mg2+ competes with Ca2+
Can therefore inhibit SR Ca2+ release
Summarise how the metabolic changes during exercise affect the fatigue levels
Increase lactate has little or no effect
Pi and Mg2+ decrease myofibrillar function
Pi reduces the free [Ca2_] in the SR
H+ may have little effect on overall E-C coupling
ADP competes with ATP for sites on RyR, thsu reducing RyR opening and Ca2+ release
increase in Mg2+ makes it harder for DHPR to open RyR
A decrease in ATP decreases RyR opening
How are ROS said to effect fatigue?
THought to cause damage to the SR leading to alterations in Ca2+ release
Could antioxidant supplementation prevent or reduce radical-induced damage to skeletal muscle?
recent studies say it has no beenfit
What is the most likely to cause fatigue, peripheral or central factors?
peripheral
Pi
decreased SR Ca2+ release
not lactate or H+ accumulation
ROS
