Nitric oxide synthase and cyclic GMP-dependent protein kinase concentrated at the neuromuscular endplate.
Nitric oxide mediates diverse functions in development and physiology of vertebrate skeletal muscle. Neuronal type nitric oxide synthase-mu is enriched in fast-twitch fibers and binds to syntrophin, a component of the sarcolemmal dystrophin glycoprotein complex. Here, we show that cyclic GMP-dependent protein kinase type I, a primary effector for nitric oxide, occurs selectively at the neuromuscular junction, in mice and rats, and both neuronal type nitric oxide synthase-mu and cyclic GMP-dependent protein kinase type I remain at skeletal muscle endplates at least two weeks following muscle denervation. Expression of neuronal type nitric oxide synthase-mu and cyclic GMP-dependent protein kinase type I are up-regulated following fusion of cultured primary myotubes. Interestingly, the highest levels of neuronal type nitric oxide synthase-mu in muscle are found complexed with dystrophin at the sarcolemma of intrafusal fibers in muscle spindles. Localization of neuronal type nitric oxide synthase-mu and cyclic GMP-dependent protein kinase type I at the neuromuscular junction suggests functions for nitric oxide and cyclic GMP in the regulation of synaptic actions of intra- and extrafusal muscle fibers.
Chao
D S
DS
Department of Physiology and Program in Biomedical Sciences, University of California at San Francisco School of Medicine, 94143-0444, U.S.A.
Silvagno
F
F
Xia
H
H
Cornwell
T L
TL
Lincoln
T M
TM
Bredt
D S
DS
D000818:Animals; D015152:Blotting, Northern; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008870:Microtubules / Q000201:enzymology; D009045:Motor Endplate / Q000201:enzymology*; D009119:Muscle Contraction / Q000502:physiology; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000201:enzymology
D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases