CAVEOLIN-3 AND NITRIC-OXIDE SYNTHASE-I IN HEALTHY AND DISEASED SKELETAL-MUSCLE

Recently, it has been shown for mouse skeletal muscle that caveolin-3 is localized in the sarcolemma and cofractionates with the original dy strophin complex (DC). In order to find out whether caveolin-3 is a fu rther component of the recently established and enlarged nitric oxide synthase (NOS) I-DC and whether members of this complex interact with and are potentially regulated by caveolin-3, mammalian and non-mammali an healthy and diseased (dystrophic) skeletal muscles were investigate d using caveolin-3, NOS I, DC components and myosin immunohistochemist ry as well as NOS I-associated diaphorase histochemistry. In healthy m ammalian skeletal muscle, caveolin-3 was colocalized with the DC compo nents in all extra-and intrafusal fibers. By contrast, NOS I was absen t in type I extrafusal fibers of certain species. In patients with Duc henne muscular dystrophy and mdx mice the components of the NOS I-DC w ere not detected in all extra-and intrafusal fiber types, while caveol in-3 was found unchanged. In healthy non-mammalian skeletal muscle, i. e. of birds, reptiles and fishes, caveolin-3 immunoreactivity was lack ing in the sarcolemma as was alpha-sarcoglycan; the other NOS I-DC com ponents were either present or absent. In conclusion, although caveoli n-3 is localized in the sarcolemma of mammalian myofibers, there are d ifferences in the microarchitecture of the components of the DC comple x and of caveolin-3 which does not appear to be linked with the NOS I- DC. Potential regulatory interactions between caveolin-3 and NOS I may nevertheless exist in those fibers where both molecules are colocaliz ed. The absence of caveolin-3 and alpha-sarcoglycan immunoreactivities in non-mammalian myofibers may suggest that the functions of these pr oteins are subserved by other components of NOS I-DC complex.