Date of Award

5-1991

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

First Advisor

Robert H. Fitts

Second Advisor

James Buchanan

Third Advisor

Thomas Eddinger

Fourth Advisor

Bela Piascek

Fifth Advisor

Brian Unsworth

Abstract

Fatigue, defined as a reduction in muscle force and power, likely results from multiple factors including alterations in excitation contraction coupling, cross-bridge events, and cell metabolism. In this thesis, the frog semitendinosus (ST) muscle was employed as a model for the study of skeletal muscle fatigue. Following the determination of the functional and histochemical properties of the ST, a stimulation protocol was developed to study the contractile and biochemical properties during recovery from fatigue. The 5 min stimulation protocol reduced peak twitch (Pt) and tetanic tension (Po) to 32% and 8.5% of initial tension, respectively. The decline in Pt was less than Po in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase followed by a slower return to the pre-fatigue tension. The maximal shortening velocity was significantly reduced at fatigue. A detailed investigation of the force-frequency relationship demonstrated a fatigue-induced shift to the left, such that optimal frequency for generating Po was reduced from 150 to 60 Hz. To investigate H+ involvement in fatigue, glass microelectrodes were constructed to directly assess the extent of fatigue-induced acidosis. The slow phase of Po recovery, CT and 1/2RT following fatigue were highly correlated to pHi recovery. These data support the hypothesis that H+ may, in part, mediate fatigue. Finally, this work employed single fiber biochemical techniques to investigate the hypothesis that the high energy phosphates and/or inorganic phosphate (Pi) mediate fatigue. ATP and phosphocreatine (PC) decreased, whereas lactate and Pi increased in the fatigued single cells. It was concluded that the decline in ATP could not limit force production, as even the lowest post-fatigue cell ATP was 100-fold higher than required for full cross-bridge activation. The significant correlation between PC and Po during recovery was likely not causative but rather directly related to the H+ content which simultaneously depressed Po and the rate of PC resynthesis. The Pi concentration increased 3-fold with stimulation. In conclusion, the results are consistent with the hypothesis that muscle fatigue during high intensity exercise is caused, in part, by an elevated cell H+ and Pi concentrations.

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