Intracellular Ca2+ transients in delta-sarcoglycan knockout mouse skeletal muscle

Biochim Biophys Acta. 2010 Mar;1800(3):373-9. doi: 10.1016/j.bbagen.2009.11.011. Epub 2009 Nov 18.


Background: delta-Sarcoglycan (delta-SG) knockout (KO) mice develop skeletal muscle histopathological alterations similar to those in humans with limb muscular dystrophy. Membrane fragility and increased Ca(2+) permeability have been linked to muscle degeneration. However, little is known about the mechanisms by which genetic defects lead to disease.

Methods: Isolated skeletal muscle fibers of wild-type and delta-SG KO mice were used to investigate whether the absence of delta-SG alters the increase in intracellular Ca(2+) during single twitches and tetani or during repeated stimulation. Immunolabeling, electrical field stimulation and Ca(2+) transient recording techniques with fluorescent indicators were used.

Results: Ca(2+) transients during single twitches and tetani generated by muscle fibers of delta-SG KO mice are similar to those of wild-type mice, but their amplitude is greatly decreased during protracted stimulation in KO compared to wild-type fibers. This impairment is independent of extracellular Ca(2+) and is mimicked in wild-type fibers by blocking store-operated calcium channels with 2-aminoethoxydiphenyl borate (2-APB). Also, immunolabeling indicates the localization of a delta-SG isoform in the sarcoplasmic reticulum of the isolated skeletal muscle fibers of wild-type animals, which may be related to the functional differences between wild-type and KO muscles.

Conclusions: delta-SG has a role in calcium homeostasis in skeletal muscle fibers.

General significance: These results support a possible role of delta-SG on calcium homeostasis. The alterations caused by the absence of delta-SG may be related to the pathogenesis of muscular dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology*
  • Electric Stimulation
  • Hindlimb
  • Humans
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Muscle Fibers, Skeletal / physiology*
  • Muscle, Skeletal / metabolism*
  • Muscular Dystrophy, Animal / genetics
  • Reference Values
  • Sarcoglycans / deficiency*
  • Signal Transduction / physiology


  • Sarcoglycans
  • Calcium