Date of Award

Summer 2014

Document Type


Degree Name

Doctor of Philosophy (PhD)


Biological Sciences

First Advisor

Fitts, Robert H.

Second Advisor

Blumenthal, Edward M.

Third Advisor

Buchanan, James T.


Intense muscle contraction induces high rates of glycolysis and ATP hydrolysis with resulting increases in inorganic phosphate (Pi) and H+, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at low (15°C) and near-physiological temperatures (30°C). At Ca2+ levels characteristic of fatigue, low pH significantly depressed force at both temperatures and in combination with Pi, depressed myofibrillar Ca2+ sensitivity and peak force to a greater extent than either metabolite alone. Individual effects of elevating H+ or Pi on velocity and power have been well characterized but collective effects less studied. Thus, the effects of simultaneously elevating H+ and Pi on velocity, power, stiffness, and rate of force development (ktr) were measured. H+ and Pi significantly depressed peak fiber power to a greater extent than either ion alone. Force-stiffness ratios significantly decreased with pH 6.2 + 30 mM Pi in both fiber types, suggesting these ions decreased the number and/or force of the high-force state of the cross-bridge. Taken with the finding that low cell pH prolongs the time in the AM*ADP state, thereby depressing velocity, the evidence suggests that H+ and Pi are significant mediators of skeletal muscle fatigue. The loss of muscle mass and function with age, or sarcopenia, is a significant public health problem. Sarcopenia is characterized by a loss of power with age, but mechanisms of such decrements or sex-specific effects are unknown. Peak force, ktr, and myofibrillar ATPase (among other parameters) were measured in muscle fibers from the vastus lateralis of young (20-30 yr) and old (>70 yr) men and women. The results demonstrate a sex-specific age effect characterized by less absolute peak force, slower cross-bridge kinetics (i.e. reduced ktr), and reduced efficiency in type I fibers from older women. Thus, age-related changes in cross-bridge function represent a potential mechanism for sarcopenia in older women.

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