Muscle Fatigue: The Cellular Aspects
Abstract
High-intensity contractile activity causes a rapid fall in peak tension or force, a reduced shortening velocity, decline in power, prolonged twitch duration, a sarcolemma action potential with a prolonged duration, reduced amplitude, and a conduction velocity that may result in conduction block. The calcium transient is characterized by a reduced amplitude and prolonged duration. What is the role of hydrogen in high-intensity exercise? It may affect E-C coupling but we do not think so. It definitely inhibits the rate of force development and calcium binding to TN-C. It also definitely inhibits the cross-bridge transition from the low to high force state. It inhibits velocity or the cross-bridge cycle rate and, therefore, decreases power and, importantly, prolongs the rate of calcium reuptake by inhibiting the sarcoplasmic reticulum calcium ATPase pump. Phosphate inhibits tension by reversing the cross-bridge transition from the low to the high force state, but it does not affect cycle rate; therefore, it does not have an effect on velocity. It may be involved in decreasing the free energy of ATP hydrolysis, which would provide less energy and, most importantly, play a role in inhibiting the sarcoplasmic reticulum calcium reuptake. Finally, what does all this mean to the athlete and how can fatigue be prevented? Basically, we do not have answers to these questions, but it is clear that the athlete is going to have to have a varied training program. If an athlete trains with one particular type of exercise, fatigue will result from other factors. Thus, a heterogeneous training program is essential. Diet is very important, and warm-up and fluid replacement are all factors that are going to be important in triggering peak performance.
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Although lactate and H+ accumulation suggest greater ATP production from glucose or glycogen, this does not always improve sprint performance.
“Previous studies indicate that although lactate and H+accumulation suggest greater ATP production from glucose or glycogen, this does not always improve sprint performance19,20.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [19]
The interplay between neuromuscular fatigue, muscle glycogen depletion, and Pi accumulation further complicates the scenario of repeated sprint performance.
“The interplay between neuromuscular fatigue, muscle glycogen depletion, and Pi accumulation further complicates this scenario19,21.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [19]
Increased H+ and lactate accumulation serves as an effective stimulus to upregulate the number of these transporters.
“Interestingly, increased H+and lactate accumulation serves as an effective stimulus to upregulate the number of these transporters19,32.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [19]
More recent evidence highlights other significant factors, such as phosphate accumulation, muscle glycogen availability, and neuromuscular impairments, all of which contribute to performance decline.
“While cellular acidosis has traditionally been seen as a major contributor to fatigue, more recent evidence highlights other significant factors, such as phosphate accumulation, muscle glycogen availability, and neuromuscular impairments, all of which contribute to performance decline19,21,37.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [19]
Phosphate accumulation, particularly the rise in inorganic phosphate, interferes with excitation-contraction coupling by disrupting calcium release from the sarcoplasmic reticulum and reducing muscle fiber calcium sensitivity.
“Phosphate accumulation, particularly the rise in inorganic phosphate, is known to interfere with excitation-contraction coupling by disrupting calcium release from the sarcoplasmic reticulum and reducing muscle fiber calcium sensitivity19,36,38.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [19]
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Self-citationMuscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate
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It is diprotonated inorganic phosphate that depresses force in skinned skeletal muscle fibers
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Schwellnus, M., Soligard, T., Alonso, J.-M., Bahr, R., Clarsen, B., Dijkstra, H. P., Gabbett, T. J., Gleeson, M., Hägglund, M., Hutchinson, M. R., et al. (2016) · British Journal of Sports Medicine · doi:10.1136/bjsports-2016-096572 · Cited by 836 · see citing works
Additive effects of beta-alanine and sodium bicarbonate on upper-body intermittent performance
Tobias, G., Benatti, F. B., de Salles Painelli, V., Roschel, H., Gualano, B., Sale, C., Harris, R. C., Lancha, A. H., & Artioli, G. G. (2013) · Amino Acids · doi:10.1007/s00726-013-1495-z · Cited by 129 · see citing works
Evaluating bioenergetic pathway contributions from single to multiple sprints
Ulupınar, S., Özbay, S., Gençoğlu, C., Ouergui, I., Öget, F., Kishalı, N. F., Kıyıcı, F., Yılmaz, H. H., & Ardigò, L. P. (2024) · Scientific Reports · doi:10.1038/s41598-024-78916-z · Cited by 14 · see citing works
- Authors
- Fitts, R. H.
- Affiliations
- Marquette University (US)
- Corresponding author
- Fitts, Robert H.
- ORCID
- Fitts, Robert H.
- Venue
- The American Journal of Sports Medicine
- Publisher
- SAGE Publications
- Published
- 1996-11
- Volume
- 24
- Issue
- 6_suppl
- Pages
- S9-S13
- ISSN
- 0363-5465 (ISSN-L)
- 1552-3365
- OpenAlex
- W2412723965
- Cited by
- 97
- References
- 10
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 8
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Sports Medicine (publishedVersion)
- PubMed (publishedVersion)
- e-Publications@Marquette (Marquette University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- muscle fatigue, high-intensity exercise, hydrogen, phosphate, calcium transients, sarcoplasmic reticulum calcium ATPase, cross-bridge cycling, excitation-contraction coupling, rate of force development, conduction block, fatigue prevention, warm-up, fluid replacement
- MeSH terms
- Action Potentials, Humans, Muscle Proteins, Physical Endurance, Physical Fitness, Muscle, Skeletal, Muscle Fibers, Skeletal, Muscle Fatigue
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