1. Fatigue During Exercise
Darrell Brooks
SENS
Presented by Marcos Michaelides

2. Definitions of fatigue
Inability to maintain a given exercise intensity.
Transient loss of work capacity – due to preceding work
 force output
slowed force development
slowed relaxation
 Vmax
Types of fatigue:
Central fatigue – CNS
Peripheral fatigue - muscle

3. Potential Sites of Fatigue
“psyche”/will
Motor neuron
Central Fatigue
Peripheral Fatigue
T-tubule
sarcolemma
SR–Ca2+ release
ATP availability
Actin-myosin interaction

4. Central Fatigue Sites
1. Supraspinal failure 2. Afferent inhibition 3. Depressed motoneuron excitability 4. Branch point excitability loss 5. Presynaptic failure

5. Central Fatigue  firing frequency of motoneurons
 free plasma tryptophan / BCAA ratio
 serotonin synthesis in brain
 dopamine release?
affects pain, mood, arousal
Davis, J.M. Carbohydrates, branched-chain amino acids and endurance: the central fatigue hypothesis. Sports Science Exchange #61, 9(2), ( (

6. Potential Sites of Fatigue

7. Potential Sites of Fatigue
1. Presynaptic conduction
2. Ac. Pot. at nm junction
3. Ac. Pot. on sarcolemma
4. Coupling to SR
5. Ca2+ release from SR
6. Ca2+ binding to troponin
7. Cross-bridge formation
8. Cross-bridge dissociation
9. Ca2+ reuptake by SR

8. Potential Sites of Fatigue
Draw and continue following meeting

9. Peripheral Fatigue
Neuromuscular junction
Impaired neuromuscular transmission
Muscle sarcolemma
Impaired conduction of action potential
*During exercise no evidence of fatigue at neuromuscular junction or sarcolemma*

10. Peripheral Fatigue
 force begins with failure of cellular mechanism(s) ‘down stream’ to muscle AP
failure involves:
excitation-contraction,
contractile elements, or both
fatigue due to:
substrate depletion
product accumulation
EC uncoupling

11. Peripheral Fatigue – Substrate depletion
Does ATP depletion cause fatigue?
exhaustive exercise depletes total muscle [ATP] to only ~70% of resting values
rate of ATP hydrolysis is  in fatigue
is ATP compartmentalized?
total amount of ATP may not be critical, rather, availability of free energy
[ATP] / ([ADP] • [Pi])

12. Peripheral Fatigue – Substrate depletion
Does PCr depletion cause fatigue?
PCr is nearly depleted within s
Creatine supplementation studies suggest:
10-30%  in resting [PCr]
no benefit to single bout exercises
delay of fatigue during repeated bouts
more rapid resynthesis of PCr

13. Peripheral Fatigue – Substrate Accumulation
Accumulation of H+ in muscle:
 affinity of troponin for Ca2+
 rate of ATP hydrolysis
 tension development by actin-myosin complex
 rates of glycolysis and glycogenolysis
bicarbonate loading improves performance
muscle pH and force recoveries are consistent

14. Peripheral Fatigue – Substrate Accumulation
Accumulation of Pi in muscle:
[Pi]i during exercise
[Pi]i slows transition from weak- to strong-binding phases
taken up by SR and diminishes Ca2+ uptake

15. Peripheral Fatigue – EC uncoupling
Calcium
Impaired excitation/relaxation
Reduced calcium release from SR
Decreased calcium sensitivity
Reduced rate of calcium uptake by SR
Due to increased Pi, ADP, H+
Decreased glycogen
Actin-myosin interaction
Impaired cross bridge cycling
Increased Pi, ADP

16. Peripheral Fatigue Experiments show that answer is complex
See
Hortemo KH, Munkvik M, Lunde PK, Sejersted OM (2013) Multiple Causes of Fatigue during Shortening Contractions in Rat Slow Twitch Skeletal Muscle. PLoS ONE 8(8): e doi: /journal.pone
Note the three phases marked with roman numbers; during the first 20 s exercise there is a prominent fall in Smax; at 100 s there is a further reduction in Smax; at 15 min there is still reduction in Smax

17. Peripheral Fatigue Experiments show that answer is complex See
Hortemo KH, Munkvik M, Lunde PK, Sejersted OM (2013) Multiple Causes of Fatigue during Shortening Contractions in Rat Slow Twitch Skeletal Muscle. PLoS ONE 8(8): e doi: /journal.pone