Intracellular Ca2+ transients in delta-sarcoglycan knockout mouse skeletal muscle.
Biochim Biophys Acta
; 1800(3): 373-9, 2010 Mar.
Article
em En
| MEDLINE
| ID: mdl-19931597
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Músculo Esquelético
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Fibras Musculares Esqueléticas
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Sarcoglicanas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Holanda