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

• Published in: Biochimica et biophysica acta Vol. 1800; no. 3; pp. 373 - 379
• Main Authors: Solares-Pérez, Alhondra, Sánchez, Jorge A., Zentella-Dehesa, Alejandro, García, María C., Coral-Vázquez, Ramón M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2010
• Subjects: Animals; Ca 2+ transients; Calcium - physiology; Electric Stimulation; Hindlimb; Humans; Intracellular calcium; Mice; Mice, Inbred Strains; Mice, Knockout; Muscle fibers; Muscle Fibers, Skeletal - physiology; Muscle, Skeletal - metabolism; Muscular dystrophy; Muscular Dystrophy, Animal - genetics; Reference Values; Sarcoglycans - deficiency; Sarcoglycan–sarcospan complex; Sarcoplasmic reticulum; Signal Transduction - physiology; DGC; δ-SG; KO; Intracellular calcium; SOC; Muscle fibers; EDL; Ca 2+ transients; SG–SSPN; Muscular dystrophy; SG; Sarcoplasmic reticulum; SR; Sarcoglycan–sarcospan complex
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2009.11.011

δ-Sarcoglycan (δ-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. Isolated skeletal muscle fibers of wild-type and δ-SG KO mice were used to investigate whether the absence of δ-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. Ca 2+ transients during single twitches and tetani generated by muscle fibers of δ-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 δ-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. δ-SG has a role in calcium homeostasis in skeletal muscle fibers. These results support a possible role of δ-SG on calcium homeostasis. The alterations caused by the absence of δ-SG may be related to the pathogenesis of muscular dystrophy.