Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy.
It is commonly accepted that skeletal muscles from dystrophin-deficient mdx mice are more susceptible than those from wild-type mice to damage from eccentric contractions. However, the downstream mechanisms involved in this enhanced force drop remain controversial. We studied the reduction of contractile force induced by eccentric contractions elicited in vivo in the gastrocnemius muscle of wild-type mice and three distinct models of muscle dystrophy: mdx, alpha-sarcoglycan (Sgca)-null, and collagen 6A1 (Col6a1)-null mice. In mdx and Sgca-null mice, force decreased 35% compared with 14% in wild-type mice. Drop of force in Col6a1-null mice was comparable to that in wild-type mice. To identify the determinants of the force drop, we measured force generation in permeabilized fibers dissected from gastrocnemius muscle that had been exposed in vivo to eccentric contractions and from the contralateral unstimulated muscle. A force loss in skinned fibers after in vivo eccentric contractions was detectable in fibers from mdx and Sgca-null, but not wild-type and Col6a1-null, mice. The enhanced force reduction in mdx and Sgca-null mice was observed only when eccentric contractions were elicited in vivo, since eccentric contractions elicited in vitro had identical effects in wild-type and dystrophic skinned fibers. These results suggest that 1) the enhanced force loss is due to a myofibrillar impairment that is present in all fibers, and not to individual fiber degeneration, and 2) the mechanism causing the enhanced force reduction is active in vivo and is lost after fiber permeabilization.
Blaauw
Bert
B
Dept. of Human Anatomy and Physiology, Univ. of Padua, Padua, Italy. bertblaauw@yahoo.com
Agatea
Lisa
L
Toniolo
Luana
L
Canato
Marta
M
Quarta
Marco
M
Dyar
Kenneth A
KA
Danieli-Betto
Daniela
D
Betto
Romeo
R
Schiaffino
Stefano
S
Reggiani
Carlo
C
D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000503:physiopathology*