The Role of Excitation-Contraction Coupling in Skeletal Muscle Fatigue

Skeletal muscle fatigue has been an area of scientific research for more than 100 years. In spite of this effort, the mechanisms underlying the phenomena are not well understood. Factors involved in fatigue may be divided into those acting on the myofilaments to decrease force production and those impairing the activation of the filaments. Because the details of the excitation-contraction coupling process have only come to light over the past 20 years, our understanding of the mechanisms by which it is impaired have lagged behind what is known about how the myofilaments are affected by fatigue. The purpose of the present study was to determine how fatigue alters a number of steps in the excitation-contraction coupling process. Specifically, studies were undertaken to 1) characterize the effects of intermittent high-frequency stimulation on the sarcolemma action potential and membrane excitability and to determine the relationship between these variables and the muscle\u27s ability to generate tension; 2) describe the alterations in the intracellular concentrations of Na+ and K+ as a result of the stimulation protocol and relate these changes to the force generating ability of the muscle; and 3) examine the effects of membrane depolarization, elevated extracellular Ca2 and decreased intracellular pH on the function of the voltage sensor of excitation-contraction coupling