DYSTROPHIN, VINCULIN, AND ACICULIN IN SKELETAL-MUSCLE SUBJECT TO CHRONIC USE AND DISUSE

Dystrophin is a subsarcolemmal protein that interacts with cytoskeleta l actin and a glycoprotein complex in the plasma membrane. One potenti al function of dystrophin is its ability to Is stabilize the sarcolemm al membrane during muscle contraction. We hypothesized 1) that chronic muscle use and disuse would alter the expression of dystrophin as a c ompensatory mechanism designed to prevent muscle damage, and 2) that o ther subsarcolemmal cytoskeletal proteins (vinculin, M-vinculin, acicu lin 60/63 kDa) that colocalize with dystrophin in muscle adherens junc tions would be changed in parallel. Chronic muscle use induced by volu ntary running or 10-Hz chronic stimulation did not alter dystrophin le vels in rat muscle. In contrast, muscle disuse induced by 6 d of micro gravity, or 7 and 21 d of denervation, increased dystrophin levels by 1.8-, 1.9- and 3.2-fold, respectively. Thus, this increase in dystroph in levels appears to be dependent on the duration of muscle disuse, in dependent of the presence of the nerve. Denervation also induced 3.3-f old increases in vinculin and aciculin 60 kDa, in parallel with dystro phin. However, in contrast to its effects on dystrophin, chronic stimu lation increased the levels of vinculin and aciculin 60 kDa by 3.4- an d 6.4-fold, respectively . Thus, both the removal and the augmentation of muscle activity resulted in increases of these two cytoskeletal pr oteins. The data indicate that the concentrations of these proteins ar e independently regulated. They further indicate that chronic muscle u se is not a stimulus for the induction of dystrophin levels, suggestin g that normal levels are sufficient for the protective effect on the s arcolemma that dystrophin may confer. The results reveal an interestin g area of muscle plasticity, and the adaptation observed may have prof ound implications for the structure and function of skeletal muscle re sponding to changes in contractile activity.