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Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles
14:02

Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles

Published on: November 1, 2012

Concerted regulation of skeletal muscle contractility by oxygen tension and endogenous nitric oxide

Jerry P Eu1, Joshua M Hare, Douglas T Hess

  • 1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 3, 2003
PubMed

Insights

Oxygen levels critically impact skeletal muscle function. This study reveals that low oxygen enhances muscle performance, while high oxygen inhibits it, with neuronal nitric oxide synthase (nNOS) playing a key regulatory role.

Area of Science:

  • Physiology
  • Biochemistry
  • Muscle Biology

Background:

  • Nitric oxide synthase (NOS) and nitric oxide (NO) are traditionally thought to inhibit skeletal muscle contractility.
  • Standard muscle contractility assessments use nonphysiological oxygen levels (95% O2) that may disrupt NO signaling.

Purpose of the Study:

  • To investigate the influence of varying oxygen tension (pO2) on skeletal muscle contractility and myocyte function.
  • To determine the role of endogenous neuronal NOS (nNOS) in mediating pO2-dependent effects on muscle performance.

Main Methods:

  • Whole-muscle contractility measurements in normal and nNOS-deficient mice.
  • Assessment of myocyte calcium flux and sarcomere shortening under different pO2 conditions.
  • Evaluation of muscle performance at physiological and nonphysiological oxygen tensions.

Main Results:

  • Skeletal muscle performance (contractility, calcium flux, sarcomere shortening) is enhanced at low physiological pO2 and inhibited at higher physiological pO2.
  • These pO2-dependent effects are dependent on endogenous nNOS activity.
  • At 95% O2, force production is increased, but NO/nitrosylation-mediated control of contractility is significantly reduced.
  • nNOS mutant muscle exhibits altered responsiveness to pO2.

Conclusions:

  • There is a fundamental role for the interplay between NO and O2 in the physiological regulation of skeletal muscle contractility.
  • The findings suggest new molecular mechanisms underlying myopathic diseases.
  • The role of NO in certain cellular systems may warrant reevaluation under physiologically relevant oxygen conditions.

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