Physiology of Nitric Oxide in Skeletal Muscle

Abstract

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.

Dietary nitrate supplementation improves sprint and high-intensity intermittent running performance

“…Nitric oxide (NO) is a gaseous signalling molecule that regulates several physiological processes that are important to exercise performance, including vasodilation, mitochondrial respiration and skeletal muscle contractility (Stamler and Meissner, 2001;Umbrello et al 2013). NO can be generated through the nitric oxide synthase (NOS)-catalysed oxidation of L-arginine and through the O 2 -independent, one-electron reduction of nitrite (NO 2 -).…”

Two weeks of watermelon juice supplementation improves nitric oxide bioavailability but not endurance exercise performance in humans

“…The free radical gas, nitric oxide (NO), is a multi-functional physiological signalling molecule that plays an integral role in skeletal muscle perfusion, metabolism, contractility and fatigue resistance [1,2]. The most recognised pathway for nitric oxide generation is the oxidation of L-arginine catalysed by the nitric oxide synthase enzymes to yield nitric oxide and L-citrulline [3].…”

nNOS regulation of skeletal muscle fatigue and exercise performance

“…The increases in intracellular Ca 2+ that occur upon muscle excitation increase basal nNOS activity several fold during contraction . Skeletal muscles express two alternatively spliced nNOS isoforms, nNOSμ and nNOSβ, both of which are expressed in fast and slow muscle types (Silvagno et al 1996;Stamler and Meissner 2001;Percival et al 2010, Figure 1). nNOSμ is scaffolded to the subsarcolemmal dystrophin glycoprotein complex (DGC) and neuromuscular junction (Brenman et al 1995(Brenman et al , 1996Adams et al 2000).…”

“…However, in human muscle approximately 75% of nNOSμ is associated with the sarcolemmal DGC, suggesting species-specific differences in nNOSμ distribution (Chang et al 1996). A pool of nNOSμ is associated with the ryanodine receptor 1 Ca 2+ release channel (RyR1) at the sarcoplasmic reticulum (SR) Ca 2+ store where it can S-nitrosylate and regulate RyR1 channel activity (Xu et al 1999;Stamler and Meissner 2001;Salanova et al 2008;Li et al 2011a, Figure 1). nNOSμ association and regulation of the ryanodine receptor is also seen in the heart (Gonzalez et al 2007).…”