Muscle fatigue during intense exercise is caused by the accumulation of inorganic phosphate (Pi) and lactic acid in the myoplasm. The myoplasmic pH decreases due to the high levels of lactic acid, reaching around 15 to 26 mmol/L, resulting in a pH drop from approximately 7 to 6.2. This decrease in pH affects the actin-myosin interactions by reducing the sensitivity to Ca++ through changes in Ca++ binding to troponin C and a decrease in the maximum number of actin-myosin interactions. Pi also plays a role in fatigue development during intense exercise as phosphate concentrations can increase from around 2 mmol/L at rest to nearly 40 mmol/L in working muscles. The elevation in Pi concentration can reduce tension through three mechanisms: (1) inhibition of Ca++ release from the sarcoplasmic reticulum (SR), (2) decreased sensitivity of contraction to Ca++, and (3) alteration in actin-myosin binding. Other factors, such as glycogen depletion, localized increase in ADP concentration, extracellular elevation of potassium (K+), and generation of oxygen free radicals, have also been linked to different forms of exercise-induced muscle fatigue. Additionally, the central nervous system plays a role in fatigue perception. Interestingly, despite fatigue, the myoplasmic ATP level does not substantially decrease. Fatigue is considered a protective mechanism to prevent muscle cell injury or death by maintaining ATP levels above critical thresholds. Most individuals stop exercising before motor unit fatigue occurs. General physical fatigue, which can involve discomfort or even pain, is believed to result from a disturbance in homeostasis caused by work. Factors contributing to the perceived discomfort may include a decrease in plasma glucose levels and accumulation of metabolites. However, the function of the motor system in the central nervous system remains unaffected. Highly motivated and trained athletes can endure the discomfort of fatigue and push themselves to the point of motor unit fatigue. The improvement in performance observed after training is influenced by motivational factors.
During intense exercise, accumulation of inorganic phosphate (Pi) and lactic acid in the myoplasm accounts for muscle fatigue. The accumulation of lactic acid, to levels as high as 15 to 26 mmol/L, decreases myoplasmic pH (from ≈7 to ≈6.2) and inhibits actin-myosin interactions. This decrease in pH reduces the sensitivity of the actin-myosin interaction to Ca++ by altering Ca++ binding to troponin C and by decreasing the maximum number of actin-myosin interactions. Pi has also been implicated as an important factor in the development of fatigue during intense exercise, inasmuch as phosphate concentrations can increase from approximately 2 mmol/L at rest to nearly 40 mmol/L in working muscle. Such an elevation in [Pi] can reduce tension by at least the following three different mechanisms: •Fig. 12.19. Aseriesofbrieftetanicstimulationsofskeletalmuscleresultinarapiddecreaseinforce(tetanicstress,exemplifiedbythe“Wholemuscle”lineinplot)thatisattributabletofatigueoffast-twitch(typeII)motorunitsinthemuscle.Undertheseconditions,however,slow-twitch(typeI)motorunitsareresistanttofatigue.3 2 1 0 10 2 3 4 5 10 20 30 Minutes Tetanus stress (kg/cm2 ) Type 1 motor units Whole muscle Type II motor units (1) inhibition of Ca++ release from the SR, (2) decrease in the sensitivity of contraction to Ca++ , and (3) alteration in actin-myosin binding. A number of other factors, including glycogen depletion from a specialized compartment, a localized increase in [ADP], extracellular elevation of [K+], and generation of oxygen free radicals, have also been implicated in various forms of exercise-induced muscle fatigue. Finally, the central nervous system contributes to fatigue, especially in how fatigue is perceived by the individual.
Regardless of whether the muscle is fatigued as a consequence of high-intensity exercise or prolonged exercise, the myoplasmic ATP level does not decrease substantially. In view of the reliance of all cells on the availability of ATP to maintain viability, fatigue has been described as a protective mechanism to minimize the risk of muscle cell injury or death. Consequently, it is likely that skeletal muscle cells have developed redundant systems to ensure that ATP levels do not drop to dangerously low levels and hence risk the viability of the cell.
Most persons tire and cease exercise long before the motor unit fatigues. General physical fatigue may be defined as a homeostatic disturbance produced by work. The basis for the perceived discomfort (or even pain) probably involves many factors. These factors may include a decrease in plasma glucose levels and accumulation of metabolites. Motor system function in the central nervous system is not impaired. Highly motivated and trained athletes can withstand the discomfort of fatigue and may exercise to the point at which some motor unit fatigue occurs. Part of the enhanced performance observed after training involves motivational factors.