1. Chapter 4. peripheral factors in neuromuscular fatigue
PF. Gardiner, Advanced neuromuscular exercise physiology

2. Neuromuscular fatigue
↓ maximal force response in spite of continued supramaximal stimulus
↑effort necessary to maintain a submaximal contractile force
During sustained submaximal muscle contraction
↑ excitation of the motor pool
simultaneous ↓ in the maximal capacity of the contractile system
Neuromuscular fatigue: a condition that develops gradually as exercise continues

3. Factors Affecting Performance

4. Sites of Fatigue Central fatigue Peripheral fatigue Neural factors
Mechanical factors
Energetics of contraction

5. Changes in contractile properties during fatigue
Jones DA et al, JP 2006

6. Changes in contractile properties during fatigue
Jones DA et al, JP 2006

7. Changes in contractile properties during fatigue
Jones DA et al, JP 2006

8. ↑ neural signals when maintaining a submaximal contractile force

9. Intramuscular factors: Interstitial K+
MAJOR factor
↑interstitial 細胞間 potassium (K+), ↓membrane excitability
critical interstitial potassium concentration at which muscle tetanic force is affected similar to that in exercising human muscles (resting: ~4 mM; exercising: mM)
sodium-potassium ATPase (Na+/K+ ATPase)
Training ↑ Na+/K+ ATPase, ↓accumulation of interstitiaI K, longer time to fatigue

10. Na, K in nerve impulse

12. Interstitial K+ and muscle force
Interstitial K+ in exercising human muscles: mM

13. Power output and interstitial K+ in human muscles

14. Intramuscular factors
ATP concentration only minor role
ATP usually NOT depleted during exercise
However, potential localized ATP depletion, especially in triad region
Na+/K+ ATPase, use ATP generated by glycolysis
↓ rate of ATP use by ↓crossbridge cycling, ↓ SR Ca2+ uptake
↑ calcium trapped in the cytoplasmic compartment
↑ magnesium (Mg2+) ↓ calcium channel opening
inorganic phosphate enter sarcoplasmic reticulum and precipitate with Ca
Minor factor : estimated <10% of maximum force

15. Exer Biochem c6-high intensity ex
X: force, : PCr, :ATP after 10s and 20 s. open: type I, close type II human muscles
Exer Biochem c6-high intensity ex

16. Fatigue mechanism – increased H+
Human muscle pH dropped from 7.05 to ~6.5 after exhaustive exercise
However, exhaustion in pH in some situations
Force usually recover faster than pH
Ca2+ release from SR NOT inhibited even at pH 6.2
H+ has much less inhibitory effect in activation of the contractile apparatus and Ca2+ release than previously assumed
Low pH could inhibit glycolytic enzyme activities
However, alkalinizers DO increase performance in HIE

17. Lactate metabolism
Whenever glycolysis produce pyruvate, lactate also produced
Pyruvate synthesis rate >> pyruvate dehydrogenase activity
Lactate dehydrogenase activity high in skeletal muscle
Fate of lactate
Leave muscle fiber via monocarboxylate transporter
Enter adjacent fiber with lower intracellular [lac]
Enter cells, used by heart, nonworking muscle (as fuel) or liver and kidney (as sources for gluconeogenesis), intercellular lactate shuttle
monocarboxylate transporter act as a symport, transfer lactate down gradient, accompanied by a H+
Lactate is NOT responsible for muscle acidity, fatigue, or soreness

18. Lactate synthesis REMOVE H+

19. Major source of H+ during exercise

20. Major mechanisms in muscle fatigue

21. Fatigue mechanisms

22. Structures other than muscle Neuromuscular transmission failure
failure of a nervous impulse to be translated into sarcolemma
Neurotransmitter depletion: acetylcholine
↓ in max force: stimulated by its motor nerve > stimulated directly to muscle
3,4-diaminopyridine ↓ force difference between indirect and direct stimulation
3,4-diaminopyridine↑acetylcholine release

23. Neuromuscular transmission failure
Postsynaptic membrane failure
Prolonged exposure to ACh  desensitize ACh receptor
Failure of axon branches to pass on action potentials
Action potential generated in axon is NOT propagated into all of the branches extending to muscle fibers

24. Difference between direct and indirect stimulation

25. Inhibition of motoneurons
Inhibition of motoneurons: ↓motoneuronal excitability, ↓ firing rates during fatigue at maximal and submaximal force
Afferent nerve (sensory nerve) signals
Demonstrated under ischemia conditions
Receptors for metabolic by-product concentrations?

26. Inhibition of motoneurons

27. Skinned muscle
skinning the muscle fibers allows us to set the intracellular concentrations of molecules
no longer a semipermeable barrier or transporter system that can become limiting