NITRIC-OXIDE SYNTHASE (NOS)-I DURING POSTNATAL-DEVELOPMENT IN RAT ANDMOUSE SKELETAL-MUSCLE

Previous studies on adult rat and mouse skeletal muscles have shown th e spatial association of nitric oxide synthase (NOS) I to the dystroph in complex (DC) in the sarcolemma of type II fibers and, in combinatio n with the NMDA receptor-1 (NMDAR-1), an accumulation of the enzyme at the neuromuscular junctions (NMJ) of this fiber type. Using immunohis tochemistry, enzyme histochemistry and alpha-bungarotoxin labeling we report here temporal relationships of NOS I, members of the DC, other components of the cortical cytoskeleton in the junctional and non-junc tional sarcolemma as well as of molecules involved in NMJ transmission of either type I or II myofibers especially in head and neck muscles during postnatal rat and mouse development. Fiber typing was performed by specific anti-myosin antibodies. Beginning with postnatal day (PD) 1 in both fiber types dystrophin, dystrophin-associated glycoproteins (DAG), beta-dystroglycan, alpha-sarcoglycan (adhalin) and spectrin we re present in; the junctional and extrajunctional sarcolemma, while ut rophin, acetylcholinesterase, alpha-bungarotoxin labeled acetylcholine receptors were concentrated in the NMJ of both fiber types. NOS I act ivity and immunoreactivity were only found in the NMJ region of type I I fibers, where NMDAR-1 appeared around PD 15. Primarily in the tongue there was no strict correlation between muscle fiber type and NOS I b ehaviour during early postnatal development, and muscle fibers not rea ctive for myosin antibodies against both fiber types were negative or positive for NOS I but always positive for the other molecules either in both the junctional and extrajunctional sarcolemma or in the NMJ on ly; later all muscle fibers of the tongue were of type II and NOS I-po sitive. Maturation of enzyme activities, immunoreactivities and AChR i ntensity depended on the respective muscle and can last until PD 50; i n the tongue and neck muscles they appeared to increase approximately until PD 20 or 25. In conclusion, in type II fibers of rat and mouse s keletal muscle all molecules with the exception of NMDAR-1 and relevan t for NOS I targeting and positioning as well as function inside and o utside the NMJ are already present at birth, but their concentrations and/or activities increase postnatally, and the adult situation appear s to be reached between the third and seventh week of postnatal life. Therefore, initial interactions between NOS I and the other molecules necessary for the formation of the NOS I-DC in and on the way to the s arcolemma presumably take place before birth.