Neuromuscular Fatigue
Muscle Physiology
420:289
Agenda
Introduction Central fatigue Peripheral fatigue Biochemistry of fatigue Recovery
Introduction Fatigue
Common definition:Any reduction in physical or mental
performance Physiological definitions:
The gradual increase in effort needed to maintain a constant outcome
The failure to maintain the required or expected outcome/task
Mechanisms Difficult to Study Many potential sites of fatigue Task specificity Central vs. peripheral factors Environment Depletion vs. accumulation Interactive nature of mechanisms Compartmentalization Training status
Potential Outcomes of Fatigue Muscle force:
Isometric or dynamic Peak force and RFD
reduced
Rate of relaxation: Reduced
Figure 15.6, McIntosh et al., 2005
Adopted from Garland et al. (1988)
Potential Outcomes of Fatigue
Muscle velocity and power: Peak and mean
reduced
McIntosh et al., 2005
Potential Outcomes of Fatigue EMG
Increases with fatigue (submaximal load) as CNS attempts to recruit more motor units
Power frequency spectrum shifts to left FT MUs fatigue resulting in greater stimulation of
ST MUs (lower threshold lower frequency)
Brooks et al., 2000
Brooks et al., 2000
Gandevia, 2001
Potential Outcomes of Fatigue
Ratings of perceived exertion Rate of fatigue
Fatigue index Wingate Time to fatigue
Mechanisms of Fatigue
Fatigue can be classified in many ways:Psychological vs. physiologicalNeuromuscular vs. metabolicCentral vs. peripheral
Agenda
Introduction Central fatigue Peripheral fatigue Biochemistry of fatigue Recovery
Central Fatigue - Introduction
Central fatigue: A progressive reduction in voluntary activation of muscle during exercise
Difficult to study however strong indirect evidence
Central Fatigue - Introduction
Central fatigue may manifest itself in several ways:Emotions and other psychological factorsAfferent input (pain, metabolites, ischemia,
muscle pressure/stretching) Intrinsic changes of the neuron
(hyperpolarization of RMP)
Figure 1, Kalmer & Cafarelli, 2004
Bottom line: Central fatigue causes neural inhibition greater voluntary effort to drive any motor unit
Evidence of Central Fatigue
Reduced motor unit firing rate and ½ relaxation time
Suggests less central drive
Figure 12, Gandevia, 2001
Evidence of Central Fatigue Concept of muscle wisdom Decline in MU firing rate does not correlate well
with decline in force As MU firing rate declines ½ relaxation time
increases (prolonged contractile mechanism) Prolongation steady force maintained with
lower MU firing rate Increased efficiency? Eventual fatigue is imminent
Evidence of Central Fatigue
Best evidence: Improvement in performance with severe fatigueSudden encouragementLast “kick” at end of race
McIntosh et al., 2005
Gandevia, 2001
Gandevia, 2001
Agenda
Introduction Central fatigue Peripheral fatigue Biochemistry of fatigue Recovery
Peripheral Fatigue
Potential sites include (but not limited to):
1. Impulse conduction of efferent neurons and terminals
2. Impulse conduction of muscle fibers
3. Excitation contraction coupling
4. Sliding of filaments
Efferent Neurons and Terminals Impulse conduction
may fail at branch points of motor axons
Unusual Branch point diameter < axon diameter
Evidence: Krnjevic & Miledi (1958)
Zhou & Shui, 2001
Krnjevic & Miledi (1958)
Rat diaphragm motor nerve Motor end plates of two fibers within same
motor unit observed Fatigue One fiber did not demonstrate
motor end plate depolarization with stimulation
Conclusion: Branch point failure
Normal branch point propagation
Branch point failure
Efferent Neurons and Terminals
Note: “Dropping out” of muscle fibers in single muscle fiber EMG studies is very rare
More research is needed
Efferent Neurons and Terminals
ACh release from axon terminals? ACh is synthesized and repackaged
quickly even during repetitive activity Safety margin: Very little ACh is required
to stimulate AP along sarcolemmaAt least 100 vescicles released/impulse
Not considered a site of peripheral fatigue
Peripheral Fatigue
Potential sites include (but not limited to):
1. Impulse conduction of efferent neurons and terminals
2. Impulse conduction of muscle fibers
3. Excitation contraction coupling
4. Sliding of filaments
Impulse Conduction Muscle Fibers
The ability of the sarcolemma to propagate APs will eventually fail during repetitive voluntary muscle actions
Attenuation is modest Mechanism: Leaking of K+ from cell
hyperpolarization of RMP
Figure 15.6, McIntosh et al., 2005
Adopted from Garland et al. (1988)
Peripheral Fatigue
Potential sites include (but not limited to):
1. Impulse conduction of efferent neurons and terminals
2. Impulse conduction of muscle fibers
3. Excitation contraction coupling
4. Sliding of filaments
Excitation-Contraction Coupling
Potential sites of fatigue: Tubular system:
T-tubulesSarcoplasmic reticulum
ECC Fatigue T-Tubules
Mechanism: Inability of AP to be propagated down t-tubule Due to pooling of K+ in t-tubule (interstitial fluid)
Recall: Muscle activation causes:
Increase of intracellular [Na+] Decrease of intracellular [K+]
Na+/K+ pump attempts to restore resting [Na+/K+] Na+/K+ pump is facilitated by:
Increased intracellular [Na+} Catecholamines
ECC Fatigue T-Tubules
T-tubule membrane surface area is small Less absolute Na+/K+ pumps Pooling of K+ in t-tubules hyperpolarizes t-
tubule RMP Time constant for movement of K+ from t-
tubules = ~ 1s Does 1 s of rest alleviate fatigue?
More mechanisms!
ECC Fatigue Sarcoplasmic Reticulum Several potential mechanisms:
Impaired SERCA function Reduced uptake of Ca2+ prolonged relaxation?
Impaired RYR channel function Reduced release of Ca2+ less crossbridges?
General rise in intracellular Ca2+ Increased uptake of Ca2+ by mitochondria
reduced mitochondrial efficiency?
Peripheral Fatigue
Potential sites include (but not limited to):
1. Impulse conduction of efferent neurons and terminals
2. Impulse conduction of muscle fibers
3. Excitation contraction coupling
4. Sliding of filaments
Sliding of Filaments
Troponin: Two potential mechanisms of fatigue
1. Decreased responsiveness: Less force at any given [Ca2+]
2. Decreased sensitivity: More [Ca2+] needed for any given force
Agenda
Introduction Central fatigue Peripheral fatigue Biochemistry of fatigue Recovery
Biochemistry of Fatigue
Metabolic fatigueDepletionAccumulation
Metabolic depletion and accumulation is related to central and peripheral fatigue
Metabolic Depletion
Phosphagens Glycogen Blood glucose
Phosphagen Depletion Phosphagens include:
ATP Creatine phosphate
CP is most immediate source of ATP due to creatine kinase
Rate of ATP: High
Capacity: Low
Phosphagen Depletion
Pattern of CP/ATP depletionCP and ATP deplete rapidlyCP continues to deplete task failureATP levels off and is preserved
Brooks, et al., 2000
Phosphagen Depletion
ATP depleted why task failure?
1. Down regulation of “non essential” ATP utilizing functions in order to maintain “essential” functions
2. Free energy theory
Phosphagen Depletion
Bottom line:CP depletion results in fatigue during high
intensity exerciseCP supplementation delays onset of task
failure
Metabolic Depletion
Phosphagens Glycogen Blood glucose
Glycogen Depletion
Recall: Glycogen is storage mechanism for CHO in muscle
Highly branched polyglucose molecule
Glycogen Depletion Glycogen depletion is associated with fatigue
during prolonged submaximal exercise Glycogen depletion is fiber type specific
depending on intensity of exercise Bottom line:
Glycogen depletion impairs ability to generate ATP at relatively fast rate task failure at moderate intensities
Supercompensation?
Metabolic Depletion
Phosphagens Glycogen Blood glucose
Low Blood Glucose
High intensity exercise increased blood sugar due to liver glycogenolysis
The rate of glycogenolysis does not match the rate of glycolysis lower blood glucose
Bottom line:Duration of exercise depends glycogen storesCHO supplementation?
Brooks, et al., 2000
Biochemistry of Fatigue
Metabolic fatigueDepletionAccumulation
Metabolic Accumulation
Inorganic phosphate Lactate and H+
Pi Accumulation
ATP ADP + Pi (HPO42-)
Effects of intracellular accumulation Inhibition of PFKReduction of ATP free energy
ADP and Pi accumulation
Inhibition of Ca2+ binding with Tn-C
Lactate and H+ Accumulation
Recall
Two possible fates for pyruvate:
1. Lactic acid
2. Mitochondria
Lactate and H+ Accumulation
When LA production > LA clearance Accumulation
At physiological pH LA dissociates a proton (H+)
As [H+] increases, pH decreasespH = -log of [H+]
www.lorenzsurgical.com/ CF_lactosorbSE_DE.shtml
H+
Lactate C3H5O3
Lactate and H+ Accumulation
Effects of intracellular H+ accumulation Inhibition of PFK Inhibition of Ca2+ binding of Tn-C Pain receptor stimulation afferent inhibition Nausea and disorientation Inhibition of O2-Hg association Inhibition of FFA release Decreased force/crossbridge Reduced Ca2+ sensitivity Inhibition of SERCA function
Lactate and H+ Accumulation
Lactate accumulation is beneficial:Lactate liver glucose via
gluconeogenesis
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Agenda
Introduction Central fatigue Peripheral fatigue Biochemistry of fatigue Recovery
Recovery - Intro
Recovery oxygen: Amt of O2 consumed in excess of normal consumption at test EPOC: Excess post-exercise oxygen consumption
Duration of recovery depends on: Intensity of exercise Duration of exercise Training status Mode of exercise
Short Term Recovery Two main
components: Fast component Slow component
ST Recovery: Fast Component
Time: 2-3 minutes VO2 declines rapidly Related to intensity of exercise Not related to duration of exercise
ST Recovery: Fast Component
Elevated metabolic rate during fast component has many functions:Resaturation of myoglobinRestore blood O2
Provide O2 for energy cost of ventilation
Provide O2 for energy cost of cardiac activity
Replenishment of ATP-PC stores
ATP-PC restoration dependent on blood flow
Short Term Recovery Two main
components: Fast component Slow component
ST Recovery: Slow Component
Time: ~ 1 hour Attenuated decline in VO2
Related to intensity and duration of exercise
ST Recovery: Slow Component
Elevated metabolic rate during slow component has many functions:Reduce core temperatureProvide O2 for energy cost of ventilationProvide O2 for energy cost of cardiac activityDecrease catecholamine levelsReplenishment of glycogenRemoval of lactate
Glycogen Repletion
Full repletion of glycogen requires several days
Glycogen depletion is dependent on:
1. Type of exercise (continuous vs. intermittent)
2. Dietary CHO consumed during repletion period
Glycogen Repletion
Glycogen repletion after continuous exercise2 hours: Insignificant repletion5 hours: Significant repletion10 hours: Greatest rate of repletion46 hours required for complete repletion with
high CHO intakeCHO vs. PRO/Fat diet
High CHO diet
PRO/Fat diet
Glycogen Repletion
Glycogen repletion after intermittent exercise30 min: Significant repletion2 hours: Greatest rate of repletion24 hours needed for complete repletion with
normal CHO intake
Glycogen Repletion
Reasons for differences b/w continuous and intermittent exercise:
1. Total glycogen depleted-Twice as much depleted with continuous-Same amount synthesized in first 24 h
2. Availability of glycogen precursors-Ex: Lactate, pyruvate, glucose-Less precursors with continuous
3. Fiber type activation-Glycogen resynthesis faster in Type II
Supercompensation
Glycogen repletion levels can be greater than pre-exercise levels with CHO loading
ST Recovery: Slow Component
Elevated metabolic rate during slow component has many functions:Reduce core temperatureProvide O2 for energy cost of ventilationProvide O2 for energy cost of cardiac activityDecrease catecholamine levelsReplenishment of glycogenRemoval of lactate
ST Recovery: Lactate
Lactate is removed during the slow component of short term recovery 30 min - 1 h
Possible fates Urine/sweat excretion (minimal) Lactate glucose Lactate protein Lactate glycogen Lactate pyruvate Kreb’s cycle CO2 + H2O