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ORCID
Access Type
Open Access Thesis
Document Type
thesis
Degree Program
Kinesiology
Degree Type
Master of Science (M.S.)
Year Degree Awarded
2019
Month Degree Awarded
May
Abstract
Skeletal muscle fatigue is the contraction-induced decline in whole muscle force or power, and can be greater in older versus young adults. Fatigue primarily results from increased metabolism elevating phosphate (Pi) and hydrogen (H+), which alters myosin-actin interactions; however, which steps of the myosin-actin cross-bridge cycle are changed and their reversibility are unclear. PURPOSE: This study sought to: 1) Examine the effects of elevated Pi and H+ on molecular and cellular function, and 2) Test the ability of deoxyadenosine triphosphate (dATP), an alternative energy to adenosine triphosphate (ATP), to reverse the contractile changes induced with high Pi and H+. METHODS: Maximal tension (force/cross-sectional area), myofilament mechanics and myosin-actin cross-bridge kinetics were measured in 214 single fibers (104 type 1) from the vastus lateralis of eight (4 men) healthy, sedentary older adults (71±1.3 years) under normal (5 mM Pi, pH 7.0), simulated fatigue (30 mM Pi, pH 6.2) and simulated fatigue with dATP conditions. RESULTS: Tension declined with high Pi and H+ in slow- (type I, 23%) and fast-contracting (type II, 28%) fibers due to fewer strongly bound myosin heads (28-48%) and slower cross-bridge kinetics (longer myosin attachment times (ton) (18-40%) and reduced rates of force production (18-30%)). Type I myofilaments became stiffer with high Pi and H+ (48%), which may have partially mitigated fatigue-induced tension reduction. Elevated Pi and H+ with dATP moderately improved force production similarly in both fiber types (8-11%) compared to high Pi and H+ with ATP. In type I fibers, high Pi and H+ with dATP returned the number of myosin heads strongly bound and ton to normal, while the rate of force production became faster than normal (16%). In type II fibers, high Pi and H+ with dATP did not change the number of myosin heads bound, but cross-bridge kinetics were 16-23% faster than normal. CONCLUSION: These results identified novel fiber-type specific changes in myosin-actin cross-bridge kinetics and myofilament stiffness that help explain fatigue-related force reduction in human single skeletal muscle fibers as well as an alternative energy source that partially to fully reverses contractile changes of elevated Pi and H+ that occur with fatigue.
DOI
https://doi.org/10.7275/13657924
First Advisor
Mark Miller
Second Advisor
Edward (Ned) Debold
Third Advisor
Jane Kent
Recommended Citation
Foster, Aurora, "Mechanisms and Mitigation of Skeletal Muscle Fatigue in Single Fibers from Older Adults" (2019). Masters Theses. 772.
https://doi.org/10.7275/13657924
https://scholarworks.umass.edu/masters_theses_2/772
Included in
Cellular and Molecular Physiology Commons, Kinesiology Commons, Laboratory and Basic Science Research Commons, Medicine and Health Sciences Commons