title: Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy.
abstract: 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.
authors.affiliation: Dept. of Human Anatomy and Physiology, Univ. of Padua, Padua, Italy. bertblaauw@yahoo.com
authors.forename: Bert
authors.initials: B
authors.lastname: Blaauw
authors.forename: Lisa
authors.initials: L
authors.lastname: Agatea
authors.forename: Luana
authors.initials: L
authors.lastname: Toniolo
authors.forename: Marta
authors.initials: M
authors.lastname: Canato
authors.forename: Marco
authors.initials: M
authors.lastname: Quarta
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dyar
authors.forename: Daniela
authors.initials: D
authors.lastname: Danieli-Betto
authors.forename: Romeo
authors.initials: R
authors.lastname: Betto
authors.forename: Stefano
authors.initials: S
authors.lastname: Schiaffino
authors.forename: Carlo
authors.initials: C
authors.lastname: Reggiani
mesh_terms: 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*