Physiology of nitric oxide in skeletal muscle

Physiol Rev. 2001 Jan;81(1):209-237. doi: 10.1152/physrev.2001.81.1.209.


In the past five years, skeletal muscle has emerged as a paradigm of "nitric oxide" (NO) function and redox-related signaling in biology. All major nitric oxide synthase (NOS) isoforms, including a muscle-specific splice variant of neuronal-type (n) NOS, are expressed in skeletal muscles of all mammals. Expression and localization of NOS isoforms are dependent on age and developmental stage, innervation and activity, history of exposure to cytokines and growth factors, and muscle fiber type and species. nNOS in particular 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 posttranslational modifications. Subcellular compartmentalization of the NOSs enables distinct functions that are mediated by increases in cGMP and by S-nitrosylation of proteins such as the ryanodine receptor-calcium release channel. Skeletal muscle functions regulated by NO or related molecules include force production (excitation-contraction coupling), autoregulation of blood flow, myocyte differentiation, respiration, and glucose homeostasis. These studies provide new insights into fundamental aspects of muscle physiology, cell biology, ion channel physiology, calcium homeostasis, signal transduction, and the biochemistry of redox-related systems.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Caveolin 3
  • Caveolins / metabolism
  • Cell Differentiation / drug effects
  • Cell Respiration / physiology
  • Drosophila Proteins*
  • Dyneins
  • Glucose / metabolism
  • Humans
  • Isoenzymes / classification
  • Isoenzymes / metabolism
  • Mammals
  • Membrane Potentials / physiology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscular Dystrophy, Duchenne / metabolism
  • Nitric Oxide / metabolism*
  • Nitric Oxide / pharmacology
  • Nitric Oxide Synthase / classification
  • Nitric Oxide Synthase / metabolism
  • Physical Exertion / physiology
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Ryanodine Receptor Calcium Release Channel / metabolism


  • Carrier Proteins
  • Caveolin 3
  • Caveolins
  • Drosophila Proteins
  • Isoenzymes
  • Ryanodine Receptor Calcium Release Channel
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Dyneins
  • Glucose