DYSTROPHIN PROTECTS THE SARCOLEMMA FROM STRESSES DEVELOPED DURING MUSCLE-CONTRACTION

The protein dystrophin, normally found on the cytoplasmic surface of s keletal muscle cell membranes, is absent in patients with Duchenne mus cular dystrophy as well as mdx (X-Linked muscular dystrophy) mice. Alt hough its primary structure has been determined, the precise functiona l role of dystrophin remains the subject of speculation. In the presen t study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly corre lated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscl e. These findings strongly support the proposition that the primary fu nction of dystrophin is to provide mechanical reinforcement to the sar colemma and thereby protect it from the membrane stresses developed du ring muscle contraction. Furthermore, the methodology used in this stu dy should prove useful in assessing the efficacy of dystrophin gene th erapy in the mdx mouse.