Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/27688
Title: Pathways of Ca2+ entry and cytoskeletal damage following eccentric contractions in mouse skeletal muscle
Authors: Zhang, BT
Whitehead, NP
Gervasio, OL
Reardon, TF
Vale, M
Fatkin, D
Dietrich, A
Yeung, EW 
Allen, DG
Keywords: Calpains
Cytoskeletal proteins
Eccentric contractions
Stretch-induced damage
Titin
Issue Date: 2012
Publisher: American Physiological Society
Source: Journal of applied physiology, 2012, v. 112, no. 12, p. 2077-2086 How to cite?
Journal: Journal of applied physiology 
Abstract: Muscles that are stretched during contraction (eccentric contractions) show deficits in force production and a variety of structural changes, including loss of antibody staining of cytoskeletal proteins. Extracellular Ca 2+ entry and activation of calpains have been proposed as mechanisms involved in these changes. The present study used isolated mouse extensor digitorum longus (EDL) muscles subjected to 10 eccentric contractions and monitored force production, immunostaining of cytoskeletal proteins, and resting stiffness. Possible pathways for Ca2+ entry were tested with streptomycin (200 μM), a blocker of stretch-activated channels, and with muscles from mice deficient in the transient receptor potential canonical 1 gene (TRPC1 KO), a candidate gene for stretch-activated channels. At 30 min after the eccentric contractions, the isometric force was decreased to 75 ± 3% of initial control and this force loss was reduced by streptomycin but not in the TRPC1 KO. Desmin, titin, and dystrophin all showed patchy loss of immunostaining 30 min after the eccentric contractions, which was substantially reduced by streptomycin and in the TRPC1 KO muscles. Muscles showed a reduction of resting stiffness following eccentric contractions, and this reduction was eliminated by streptomycin and absent in the TRPC1 KO muscles. Calpain activation was determined by the appearance of a lower molecular weight autolysis product and μ-calpain was activated at 30 min, whereas the muscle-specific calpain-3 was not. To test whether the loss of stiffness was caused by titin cleavage, protein gels were used but no significant titin cleavage was detected. These results suggest that Ca2+ entry following eccentric contractions is through a stretch-activated channel that is blocked by streptomycin and encoded or modulated by TRPC1.
URI: http://hdl.handle.net/10397/27688
ISSN: 8750-7587
EISSN: 1522-1601
DOI: 10.1152/japplphysiol.00770.2011
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