TY - JOUR
T1 - Intracellular Ca2+ transients in delta-sarcoglycan knockout mouse skeletal muscle
AU - Solares-Pérez, Alhondra
AU - Sánchez, Jorge A.
AU - Zentella-Dehesa, Alejandro
AU - García, María C.
AU - Coral-Vázquez, Ramón M.
N1 - Funding Information:
This work was supported by CONACyT grants 60880 (J.S), 82667 (M.C.G), and 55199 (R.M.C.V.). R.M.C.V. was supported by grant 2006/1A/I/078 from IMSS . A.S.P. was supported during the Ph.D. program (Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México) by scholarships from Consejo Nacional de Ciencia y Tecnología, México (223377), IMSS and Dirección General de Estudios de Postgrado at Instituto de Investigaciones Biomédicas, UNAM. We thank Ascención Hernández for technical support.
PY - 2010/3
Y1 - 2010/3
N2 - Background: 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 Ca2+ 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 δ-SG KO mice were used to investigate whether the absence of δ-SG alters the increase in intracellular Ca2+ during single twitches and tetani or during repeated stimulation. Immunolabeling, electrical field stimulation and Ca2+ transient recording techniques with fluorescent indicators were used. Results: Ca2+ 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 Ca2+ 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. Conclusions: δ-SG has a role in calcium homeostasis in skeletal muscle fibers. General significance: 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.
AB - Background: 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 Ca2+ 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 δ-SG KO mice were used to investigate whether the absence of δ-SG alters the increase in intracellular Ca2+ during single twitches and tetani or during repeated stimulation. Immunolabeling, electrical field stimulation and Ca2+ transient recording techniques with fluorescent indicators were used. Results: Ca2+ 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 Ca2+ 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. Conclusions: δ-SG has a role in calcium homeostasis in skeletal muscle fibers. General significance: 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.
KW - Ca transients
KW - Intracellular calcium
KW - Muscle fibers
KW - Muscular dystrophy
KW - Sarcoglycan-sarcospan complex
KW - Sarcoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=77049084960&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2009.11.011
DO - 10.1016/j.bbagen.2009.11.011
M3 - Artículo
C2 - 19931597
SN - 0304-4165
VL - 1800
SP - 373
EP - 379
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -