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


CONCLUSIONS
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.
Solares-Pérez
Alhondra
A
Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría, CMN Siglo XXI-IMSS, México, D.F., Mexico.
Sánchez
Jorge A
JA
Zentella-Dehesa
Alejandro
A
García
María C
MC
Coral-Vázquez
Ramón M
RM
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004558:Electric Stimulation; D006614:Hindlimb; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics; D012016:Reference Values; D049031:Sarcoglycans / Q000172:deficiency*; D015398:Signal Transduction / Q000502:physiology
D049031:Sarcoglycans; D002118:Calcium