Muscle fatigue related to long-term, repeat muscle contraction is caused by a calcium leak inside muscle cells that contributes to weakened muscle force and activates a protein-digesting enzyme which damages muscle fibers, according to a study published by a team of Columbia University Medical Center and Appalachian State University physiologists.
Findings indicate that reduced task execution and muscle damage can persist for days or weeks when exhaustive exercise is performed.
Although different from cumulative trauma disorders (CTDs), localized fatigue has been recognized by ergonomists as a contributor to discomfort/impaired performance and a potential precursor to CTDs. This study reinforces the concept that repeat event exposures (muscle contractions) may interfere with the normal tissue recovery process to produce disproportional responses and eventually an injury.
The researchers also developed an experimental drug to control cell calcium flow. It was found to alleviate muscle fatigue in mice after exercise, but has not been tested in humans.
Study Design
Experiment Procedure
Mice were induced to swim twice daily for 90 minutes for three weeks. The mice also performed a once-weekly treadmill running protocol.
Chemical Analysis
From hind-limb muscle, RyR1 was immunoprecipitated and analyzed for components after exercise. Over time, a progressive PKA phosphorylation of RyR1 was seen. High intensity exercise produced a remodeling of the RyR1macromolecular complex consisting of:
- PKA hyperphosphorylation at Ser-2844
- RyR1 S-nitrosylation
- PDE4D3 depletion
- Calstabin1 depletion
The authors felt that this change was consistent with leaky RyR1/Ca2+ release channels.
After three days of rest, only partial recovery occurred.
Drug Test
S107, a drug that would prevent calstabin1 depletion from the RyR1 complex (plugs the leak), was given to the mice 4 days prior to a 3 week swimming routine. Follow up testing showed that the drug prevented muscle damage, improved muscle function and increased exercise capacity.
Human Crossover Application
Twelve trained athletes performed 3 hours of cycling over 3 consecutive days at 70 percent VO2max. Thigh muscle biopsies were taken before and after the aerobic exercise (there were 6 controls). By day 3, the RyR1 channel complex remodeled in a manner similar to the mice.
The experimental drug was not given to the human subjects.
Other Points
Lactic acid build up, a theory proposed to explain the existence of muscle fatigue, has been recently discredited by physiologists. Alteration in normal calcium flow is more consistent with known mechanisms of muscle contraction.
The Bottom Line – How This Applies To Ergonomists
Ergonomists have long felt muscle fatigue is a precursor to work related musculoskeletal disorders (WMSDs). If fatigue is controlled, WMSDs are avoided. This study provides a molecular justification for this opinion.
Prior findings by ergonomists involving localized fatigue dovetail with this research including:
- Localized fatigue leads to pain and impairs work performance (Corlett and Bishop 1978, Harms-Ringdahl 1986)
- Localized fatigue is related to the intensity and duration of work and can occur within seconds, minutes or hours (Rohmert 1973)
- Recovery from localized fatigue can occur within minutes, hours or, in extreme cases, a few days (Rohmert 1973)
- As muscle force drops below 15 percent of maximum exertion, the time duration prior to exhaustion and discomfort increases significantly; however, physiological changes and pain may result from prolonged or repeated exertions at lower levels (Armstrong, 2002)
Article Title: Remodeling of ryanodine receptor complex causes “leaky” channels”: A molecular mechanism for decreased exercise capacity
Publication: Proceedings of the National Academy of Sciences, 105:6 2198-2202, 2008
Online: http://www.pnas.org/cgi/content/full/105/6/2198
Authors: A M Bellinger, S Reiken, M Dura, P W Murphy, S X Deng, D W Landry, D Nieman, S E Lehnart, M Samaru, A LaCampagne, and A R Marks
This article originally appeared in The Ergonomics Report™ on 2008-02-27.