title: Dystrophin is not a specific component of the cardiac costamere.
abstract: Dystrophin is a key component of the subsarcolemmal skeleton of muscle cells, and lack of dystrophin is the direct cause of Duchenne muscular dystrophy. In skeletal muscle, dystrophin is reported to be localized specifically at costameres, transversely oriented riblike subsarcolemmal plaques that mechanically couple the contractile apparatus to the extracellular matrix. Costameres are characteristically rich in vinculin and are prominent in cardiac as well as skeletal muscle. To define the precise spatial relationship between dystrophin in relation to the costamere in cardiac muscle, we applied high-resolution single- and double-immunolabeling techniques, under a range of preparative conditions, with visualization of vinculin (as a costamere marker) and dystrophin by confocal microscopy and by the freeze-fracture cytochemical technique, fracture label. Immunoconfocal visualization revealed dystrophin as a continuous uniform layer at the cytoplasmic surface of the peripheral plasma membrane of the rat cardiac myocyte at both costameric and noncostameric regions. The pattern of labeling was reproducible with three different antibodies and was independent of time and antibody concentration. Platinum/carbon replicas and thin sections of fracture-label specimens permitted high-resolution visualization of the distribution of dystrophin in plane views of the freeze-fractured plasma membrane and in relation to the sarcomeric banding patterns of the underlying 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 contrast to skeletal muscle, dystrophin in cardiac muscle is not exclusively a component of the costamere.
authors.affiliation: Imperial College School of Medicine, National Heart and Lung Institute, London, England.
authors.forename: S
authors.initials: S
authors.lastname: Stevenson
authors.forename: S
authors.initials: S
authors.lastname: Rothery
authors.forename: M J
authors.initials: MJ
authors.lastname: Cullen
authors.forename: N J
authors.initials: NJ
authors.lastname: Severs
mesh_terms: D000818:Animals; D016189:Dystrophin / Q000032:analysis* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D016189:Dystrophin