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

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

Author information

1
Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría, CMN Siglo XXI-IMSS, México, D.F., Mexico.

Abstract

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.

PMID:
19931597
DOI:
10.1016/j.bbagen.2009.11.011
[Indexed for MEDLINE]

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