NO message from muscle

The synthesis of the free radical gas nitric oxide (NO) is catalyzed by the enzyme NO synthase (NOS). NOS converts arginine and molecular oxygen to NO and citrulline in a reaction that requires NADPH, FAD, FMN, and tetrahydro biopterin as cofactors. Three types of NOS have been identified by molecula r cloning. The activity of the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) is Ca2+/calmodulin-dependent,whereas that the i nducible NOS (iNOS) is Ca2+-insensitive. The predominant NOS isoform in ske letal muscle is nNOS. It is present at the sarcolemma of both extra- and in trafusal muscle fibers. An accentuated accumulation of nNOS is found in the endplate area. This strict sarcolemmal localization of nNOS is due its ass ociation with the dystrophin-glycoprotein complex, which is mediated by the syntrophins. The activity of nNOS in skeletal muscle is regulated by devel opmental, myogenic, and neurogenic influences. NO exerts several distinct e ffects on various aspects of skeletal muscle function, such as excitation-c ontraction coupling, mitochondrial energy production, glucose metabolism, a nd autoregulation of blood flow. Inside the striated muscle fibers, NO inte racts directly with several classes of proteins, such as soluble guanylate cyclase, ryanodine receptor, sarcoplasmic reticulum Ca2+- ATPase, glycerald ehyde-3-phosphate dehydrogenase, and mitochondrial respiratory chain comple xes, as well as radical oxygen species. In addition, NO produced and releas ed by contracting muscle flbers diffuses to nearby arterioles where it acts to inhibit reflex sympathetic vasoconstriction. Microsc. Res. Tech. 55:148 -153, 2001. (C) 2001 Wiley-Liss, Inc.