This revised application is based on two unexpected findings from the Principal Investigator's recent immobilization studies. They found that 3-5 weeks of splinting did not affect either the strength or the fatigability of the elbow flexor muscles with low-force contractions. The absence of an effect on first dorsal interosseus was probably due to immobilization-induced enhancement of excitation-contraction coupling. The latter observation underscores the important role of excitation-contraction coupling and in endurance time of low-force contractions. They hypothesize that an adequately restrained first dorsal interosseus will exhibit the same adaptations with immobilization as the elbow flexor muscles and that, for both muscles, there will be a close association between changes in the efficacy of excitation-contraction coupling and in the endurance time of low-force contractions during and after immobilization. The specific aims are: (1) to determine the effect of different levels of muscle activity during immobilization on size and strength of the first dorsal interosseus muscle; and (2) to identify the time course and magnitude of immobilization-induced changes in indices of excitation-contraction coupling and the fatigability of the first dorsal interosseus and elbow flexor muscles. To address Aim 1, they will record the level of EMG in first dorsal interosseus during 4 weeks of immobilization in three groups of subjects and measure the post-immobilization size and performance of the hand muscle. The three groups of subjects will exhibit different levels of muscle activity during immobilization so that it should be possible to identify the threshold below which muscle activity must decline before immobilization affects size and performance. To address Aim 2, they will measure the force-frequency relationship, the MRI-based transverse relaxation time, and the endurance time for sustained, low-force contractions before, during and after 4 weeks of limb immobilization and after 4 weeks of recovery in the first dorsal interosseus and elbow flexor muscles. The intent is that knowledge gained from these studies will contribute to understanding the neuromuscular mechanisms that underlie muscle fatigue and will have relevance for neurologic, orthopedic, and rehabilitation medicine.