α1-Syntrophin-deficient mice exhibit impaired muscle force recovery after osmotic shock

Muscle Nerve. 2014 May;49(5):728-35. doi: 10.1002/mus.23990.

Abstract

Introduction: α1-syntrophin, a member of the dystrophin complex, recruits membrane molecules, including aquaporin-4, at the sarcolemma. The physiological functions of α1-syntrophin are poorly understood.

Methods: We examined the physiological characteristics of α1-syntrophin-deficient muscles under osmotic stress conditions to test the possibility that mutant muscles are less tolerant of osmotic shock.

Results: Isolated muscle bundles from mutant mice showed markedly reduced force production after hypo-osmotic shock. In addition, the mutant muscle bundles showed delayed recovery of specific gravity after being exposed to hypo-osmotic conditions. Two consecutive exercise tests on the treadmill revealed their performance in the second test was significantly lower than for wild-type mice. Furthermore, mutant mice had higher serum lactate concentrations after treadmill exercise.

Conclusions: Although the lack of α1-syntrophin from the sarcolemma does not lead to muscle degeneration, our results suggest that it may be partly involved in the pathophysiology of dystrophin-deficient Duchenne muscular dystrophy.

Keywords: Duchenne muscular dystrophy; aquaporin-4; fatigue; osmotic regulation; α1-syntrophin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / deficiency
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology*
  • Disease Models, Animal
  • In Vitro Techniques
  • Lactic Acid / blood
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Muscle Fatigue / genetics*
  • Muscle Fatigue / physiology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / physiology*
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • Muscle Strength / genetics
  • Muscle Strength / physiology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology*
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / physiopathology*
  • Osmotic Pressure / physiology*

Substances

  • Calcium-Binding Proteins
  • Membrane Proteins
  • Muscle Proteins
  • syntrophin alpha1
  • Lactic Acid