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ORCID

0000-0002-2780-8371

Document Type

Open Access 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.

First Advisor

Mark Miller

Second Advisor

Edward (Ned) Debold

Third Advisor

Jane Kent

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