Fatigue During Exercise Darrell Brooks SENS Presented by Marcos Michaelides

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

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

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

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), 1996. (www.gssiweb.com) (http://www.gssiweb.com/reflib/refs/34/d00000002000001cb.cfm)

Potential Sites of Fatigue

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

Potential Sites of Fatigue Draw and continue following meeting

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*

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

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])

Peripheral Fatigue – Substrate depletion Does PCr depletion cause fatigue? PCr is nearly depleted within 10-15 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

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

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

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

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): e71700. doi:10.1371/journal.pone.0071700 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071700 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

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): e71700. doi:10.1371/journal.pone.0071700 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071700