EFFECTS OF LIMB IMMOBILIZATION ON CYTOCHROME-C-OXIDASE ACTIVITY AND GLUT4 AND GLUT5 PROTEIN EXPRESSION IN HUMAN SKELETAL-MUSCLE

1. We investigated the effects of limb immobilization (for 1 or 6 week s) in a long leg cast after a closed tibial fracture (n=11). Biopsies of vastus lateralis were taken on admission and after either 1 week (n =5) or 6 weeks (n=6) and analysed for muscle fibre type characteristic s, cytochrome c oxidase activity and the abundance of GLUT4 and GLUTS hexose transporters. 2. After 1 week of immobilization there was a sig nificant decrease (8%) in the cross-sectional area of type I, but not type II, muscle fibres and in the protein-DNA ratio (16%) compared wit h the initial biopsy, Six weeks of immobilization led to further muscl e atrophy compared with the initial biopsy and a further reduction in the cross-sectional area of both type I and II fibres (29% and 36% dec rease respectively) and in the protein-DNA ratio (25%). No changes wer e observed in the free leg after 1 week. However, at the end of the 6 week study period, the cross-sectional area of both type I and II fibr es of the free leg were increased (7% and 5%) and there was significan t increase in the protein-DNA ratio (14%), indicating a net increase i n muscle protein content. 3. Assay for cytochrome c oxidase activity s howed significant reduction after 1 (30%) or 6 weeks (36%) of immobili zation, reflecting a reduced capacity for oxidative metabolism, No sig nificant changes in activity were observed in muscle from the free leg after 1 or 6 weeks of study. 4. The concentrations of GLUT4 and GLUT5 protein were determined by Western blot analysis, Limb immobilization induced a marked (50%) reduction in muscle GLUT4 protein concentratio n after 1 week that persisted for 6 weeks. A transient but significant increase (approximately twofold) in GLUT4 concentration was detected in muscle from the free leg after 1 week, but this returned to preimmo bilization values at 6 weeks. Unlike GLUT4, no significant changes in the abundance of the GLUT5 protein were detected in either the immobil ized or free leg at the end of the 1 or 6 week periods. 5. The present findings indicate that disuse rapidly induces a selective loss of act ivity and abundance of some non-myofibrillar proteins in humans, The d ecrease in GLUT4 protein abundance and cytochrome c oxidase activity d uring muscle disuse is consistent with a decreased capacity for glucos e uptake and with a lower oxidative potential of inactive muscle, The lack of any major changes in GLUTS protein abundance during limb immob ilization indicates that the expression of some non-myofibrillar prote ins is differentially regulated in response to muscle disuse.