Differential distribution of dystrophin and beta-spectrin at the sarcolemma of fast twitch skeletal muscle fibers

We used double label immunofluorescence and confocal microscopy to examine the organization of beta-spectrin and dystrophin at the sarcolemma of fast twitch myofibers in the Extensor Digitorum Longus (EDL) of the rat. Both be ta-spectrin and dystrophin are concentrated in costameres, a rectilinear sa rcolemmal array composed of longitudinal strands and transverse elements ov erlying Z and M lines. In contrast, intercostameric regions, lying between these linear structures, contain significant levels of dystrophin but littl e detectable beta-spectrin. The dystrophin-associated proteins, syntrophin and beta-dystroglycan, are also concentrated at costameres but, like dystro phin, are present in intercostameric regions as well. Dystrophin is present at costameres and intercostameric regions in fast twitch muscles of the mo use but is absent from all regions of the sarcolemma in the mdx mouse, whic h lacks dystrophin. Areas of the sarcolemma near myonuclei also contain dys trophin without beta-spectrin, consistent with the idea that the distributi on of dystrophin at the sarcolemma is not dependent on beta-spectrin. We co nclude that dystrophin is present under all areas of the sarcolemma. The in creased fragility of the sarcolemma in patients with Duchennes muscular dys trophy may be explained in part by the absence of dystrophin not only from costameres, but also from intercostameric regions.