Dystrophin is a subsarcolemmal protein that interacts with cytoskeletal actin and a glycoprotein complex in the plasma membrane. One potential function of dystrophin is its ability to stabilize the sarcolemmal membrane during muscle contraction. We hypothesized 1) that chronic muscle use and disuse would alter the expression of dystrophin as a compensatory mechanism designed to prevent muscle damage, and 2) that other subsarcolemmal cytoskeletal proteins (vinculin, M-vinculin, aciculin 60/63 kDa) that colocalize with dystrophin in muscle adherens junctions would be changed in parallel. Chronic muscle use induced by voluntary running or 10-Hz chronic stimulation did not alter dystrophin levels in rat muscle. In contrast, muscle disuse induced by 6 d of microgravity, or 7 and 21 d of denervation, increased dystrophin levels by 1.8-, 1.9- and 3.2-fold, respectively. Thus, this increase in dystrophin levels appears to be dependent on the duration of muscle disuse, independent of the presence of the nerve. Denervation also induced 3.3-fold increases in vinculin and aciculin 60 kDa, in parallel with dystrophin. However, in contrast to its effects on dystrophin, chronic stimulation increased the levels of vinculin and aciculin 60 kDa by 3.4- and 6.4-fold, respectively. Thus, both the removal and the augmentation of muscle activity resulted in increases of these two cytoskeletal proteins. The data indicate that the concentrations of these proteins are independently regulated. They further indicate that chronic muscle use is not a stimulus for the induction of dystrophin levels, suggesting that normal levels are sufficient for the protective effect on the sarcolemma that dystrophin may confer. The results reveal an interesting area of muscle plasticity, and the adaptation observed may have profound implications for the structure and function of skeletal muscle responding to changes in contractile activity.
Department of Biology and School of Physical Education, York University, North York, Ontario, CANADA M3J 1P3
Submitted for publication January 1995.
Accepted for publication June 1995.
We are grateful to Dr. R.G. Worton, Genetics Dept., The Hospital for Sick Children, Toronto, Canada, for the original donation of a dystrophin antibody, to M.A. Glukhova, currently at the Laboratoire de Physiopathologie du Développement, Ecole Normale Supérieure, Paris, France, for the donation of anti-vinculin/M-vinculin VIIF9 monoclonal antibodies, and to Dr. A. Belkin, Dept. of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, USA, for providing the anti-aciculin 60/63 kDa XIVF8 monoclonal antibody. This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Canadian Space Agency, and the Heart and Stroke Foundation of Ontario.
Address for correspondence: Dr. David A. Hood, Department of Biology, York University, 4700 Keele St., North York, Ont., Canada M3J 1P3.