DYSTROPHIN IS NOT A SPECIFIC COMPONENT OF THE CARDIAC COSTAMERE

Dystrophin is a key component of the subsarcolemmal skeleton of muscle cells, and lack of dystrophin is the direct cause of Duchenne muscula r dystrophy. In skeletal muscle, dystrophin is reported to be localize d specifically at costameres, transversely oriented riblike subsarcole mmal plaques that mechanically couple the contractile apparatus to the extracellular matrix. Costameres are characteristically rich in vincu lin and are prominent in cardiac as well as skeletal muscle. To define the precise spatial relationship between dystrophin in relation to th e costamere in cardiac muscle, we applied high-resolution single- and double-immunolabeling techniques, under a range of preparative conditi ons, with visualization of vinculin (as a costamere marker) and dystro phin by confocal microscopy and by the freeze-fracture cytochemical te chnique, fracture label. Immunoconfocal Visualization revealed dystrop hin as a continuous uniform layer at the cytoplasmic surface of the pe ripheral plasma membrane of the rat cardiac myocyte at both costameric and noncostameric regions. The pattern of labeling was reproducible w ith three different antibodies and was independent of time and antibod y concentration. Platinum/carbon replicas and thin sections of fractur e-label specimens permitted high-resolution visualization of the distr ibution of dystrophin in plane Views of the freeze-fractured plasma me mbrane and in relation to the sarcomeric banding patterns of the under lying myofibrils. These results confirmed no preferential association of dystrophin with costameres or with any region of the sarcomeres of underlying myofibrils in rat cardiac tissue. We conclude that in contr ast to skeletal muscle, dystrophin in cardiac muscle is not exclusivel y a component of the costamere.