Physiology of nitric oxide in skeletal muscle

In the past five years, skeletal muscle has emerged as a paradigm of "nitri c oxide" (NO) function and redox-related signaling in biology. All major ni tric oxide synthase (NOS) isoforms, including a muscle-specific splice vari ant of neuronal-type (n) NOS, are expressed in skeletal muscles of all mamm als. Expression and localization of NOS isoforms are dependent on age and d evelopmental stage, innervation and activity, history of exposure to cytoki nes and growth factors, and muscle fiber type and species. nNOS in particul ar may show a fast-twitch muscle predominance. Muscle NOS localization and activity are regulated by a number of protein-protein interactions and co- and/or post-translational modifications. Subcellular compartmentalization o f the NOSs enables distinct functions that are mediated by increases in cGM P and by S-nitrosylation of proteins such as the ryanodine receptor-calcium release channel. Skeletal muscle functions regulated by NO or related mole cules include force production (excitation-contraction coupling), autoregul ation of blood flow, myocyte differentiation, respiration, and glucose home ostasis. These studies provide new insights into fundamental aspects of mus cle physiology, cell biology, ion channel physiology, calcium homeostasis, signal transduction, and the biochemistry of redox-related systems.