Mechanisms and management of fatigue in health and disease: symposium introduction.

Exercise intolerance is a condition commonly experienced by both the healthy and those with disease. Yet we have only a limited understanding of the underlying mechanisms and, consequently, the management of this condition. In this Symposium, a major objective was to address the role of the muscle cell in weakness and fatigue. We have focused on addressing the advances made in characterizing the basis of muscle cell contractility with particular respect to the processes and proteins involved in excitation and contraction, and how these processes can be modified during repetitive activity. Three reviews are provided on this subject. Each addresses a specific link in the cascade of events from neural activation of the muscle to the generation of force. In the first review the processes involved in signal transduction in the sarcolemma and T-tubule, and which regulate membrane excitability, are examined. The second review analyzes the sarcoplasmic reticulum regulation of the intracellular messenger that controls the myofibrillar complex, namely free calcium. The final review in this series deals with the events regulating actin-myosin behaviour and the mechanical response. All reviews place special emphasis on how different sites can be modified by repetitive activity and, as a consequence, how they can represent a potential source of fatigue. Since it is important to understand the nature, manifestations, and measurement of weakness and fatigue, a comprehensive review on these topics is also provided.