Oxidative capacity and fatigability in run-trained malignant hyperthermia-susceptible mice

Muscle Nerve. 2012 Apr;45(4):586-96. doi: 10.1002/mus.22343.

Abstract

Introduction: The purpose of this study was to test the hypothesis that malignant hyperthermia model mice (RyR1Y522S/wt) are more vulnerable to exercise-induced muscle injury and fatigability and adapt less to run training.

Methods: After 6 weeks of voluntary wheel running, we measured anterior crural muscle fatigability, muscle injury, and cytochrome oxidase (COX) and citrate synthase (CS).

Results: Although RyR1Y522S/wt mice ran without undergoing MH episodes, they ran 42% less distance than wild-type (WT) mice. Muscles from WT mice exhibited increased fatigue resistance and COX content after training. Muscles from RyR1Y522S/wt mice demonstrated no significant change in fatigability or COX and CS after training. However, muscles from RyR1Y522S/wt mice displayed less intrinsic fatigability and greater COX/CS content and muscle damage than WT mice.

Conclusions: RyR1Y522S/wt mice can run without having rhabdomyolysis, and their inability to adapt to training appears to stem from intrinsic enhancement of mitochondrial enzymes and fatigue resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aerobiosis
  • Animals
  • Blotting, Western
  • Citrate (si)-Synthase / metabolism
  • Disease Susceptibility
  • Electron Transport Complex IV / metabolism
  • Female
  • Hypertension, Malignant / metabolism*
  • Hypertension, Malignant / physiopathology*
  • Isometric Contraction / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria, Muscle / metabolism
  • Muscle Fatigue / physiology*
  • Muscle Fibers, Skeletal / pathology
  • Muscle Strength / physiology
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiopathology*
  • Myosin Heavy Chains / metabolism
  • Organ Size / physiology
  • Oxidation-Reduction
  • Physical Conditioning, Animal / physiology*
  • Physical Endurance / physiology
  • Polymerase Chain Reaction
  • Running / physiology
  • Ryanodine Receptor Calcium Release Channel / genetics

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Electron Transport Complex IV
  • Citrate (si)-Synthase
  • Myosin Heavy Chains