DIFFERENCES IN THE LOCALIZATION OF THE POSTSYNAPTIC NITRIC-OXIDE SYNTHASE-I AND ACETYLCHOLINESTERASE SUGGEST A HETEROGENEITY OF NEUROMUSCULAR-JUNCTIONS IN RAT AND MOUSE SKELETAL-MUSCLES

Recently, nitric oxide synthase (NOS)I has been identified in skeletal muscle fibers, where the enzyme is found to be associated to the sarc olemma by the alpha 1-syntrophin-dystrophin complex. It has, however, been proposed that a substantial proportion of NOS I at the neuromuscu lar junction (NMJ) is of neuronal origin. We have, therefore, investig ated the distribution of NOS I in NMJ of normal rats and mice as well as mdx mice which lack dystrophin and, consequently, NOS I in the sarc olemma region by enzyme histochemical and immunohistochemical techniqu es. Sites of NOS I accumulation, evident at NMJ of healthy animals, we re absent in mdx mice, indicating a predominently, if not exclusively, postsynaptic localization of NOSI at NMJ. Moreover, simultaneous demo nstration of acetylcholinesterase (AChE) activity revealed a heterogen eity of NMJ in rat and mouse skeletal muscles: type I showed only AChE activity and was found to predominate; type II was spatially separate d from the AChE-positive NMJ, occurred less frequently and contained b oth AChE activity and NOS I. These data suggest that type II NMJ are p rovided with additional regulatory mechanisms, such as free radical si gnaling by the NOS I-derived NO which may exert modulatory effects on the choline acetyltransferase/ACh/AChE pathway. Furthermore, type II m ay represent those NMJ where recently glutamate-gated NMDA-type Ca2+ c hannels have been described, which in analogy to those in the nervous system may serve also in skeletal muscle fibers as NOS I activators.