Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle

Justin Percival, Kendra N E Anderson, Paul Huang, Marvin E. Adams, Stanley C. Froehner

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Signaling via the neuronal NOS (nNOS) splice variant nNOSμ is essential for skeletal muscle health and is commonly reduced in neuromuscular disease. nNOSμ is thought to be the predominant source of NO in skeletal muscle. Here we demonstrate the existence of what we believe to be a novel signaling pathway, mediated by the nNOS splice variant nNOSβ, localized at the Golgi complex in mouse skeletal muscle cells. In contrast to muscles lacking nNOSμ alone, muscles missing both nNOSμ and nNOSβ were severely myopathic, exhibiting structural defects in the microtubule cytoskeleton, Golgi complex, and mitochondria. Skeletal muscles lacking both nNOSμ and nNOSβ were smaller in mass, intrinsically weak, highly susceptible to fatigue, and exhibited marked postexercise weakness. Our data indicate that nNOSβ is a critical regulator of the structural and functional integrity of skeletal muscle and demonstrate the existence of 2 functionally distinct nNOS microdomains in skeletal muscle, created by the differential targeting of nNOSμ to the sarcolemma and nNOSβ to the Golgi. We have previously shown that sarcolemmal nNOSμ matches the blood supply to the metabolic demands of active muscle. We now demonstrate that nNOSβ simultaneously modulates the ability of skeletal muscle to maintain force production during and after exercise. We conclude therefore that nNOS splice variants are critical regulators of skeletal muscle exercise performance.

Original languageEnglish
Pages (from-to)816-826
Number of pages11
JournalJournal of Clinical Investigation
Volume120
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

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Vasoconstriction
Fatigue
Skeletal Muscle
Golgi Apparatus
Muscles
Sarcolemma
Neuromuscular Diseases
Cytoskeleton
Microtubules
Muscle Cells
Mitochondria
Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle. / Percival, Justin; Anderson, Kendra N E; Huang, Paul; Adams, Marvin E.; Froehner, Stanley C.

In: Journal of Clinical Investigation, Vol. 120, No. 3, 01.03.2010, p. 816-826.

Research output: Contribution to journalArticle

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