title: Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats.
abstract: The dystrophin–glycoprotein complex (DGC) provides an essential link from the muscle fibre cytoskeleton to the extracellular matrix. In dystrophic humans and mdx mice, mutations in the dystrophin gene disrupt the structure of the DGC causing severe damage to muscle fibres. In frog muscles, transmission of force laterally from an activated fibre to the muscle surface occurs without attenuation, but lateral transmission of force has not been demonstrated in mammalian muscles. A unique ‘yoke' apparatus was developed that attached to the epimysium of muscles midway between the tendons and enabled the measurement of lateral force. We now report that in muscles of young wild-type (WT) mice and rats, compared over a wide range of longitudinal forces, forces transmitted laterally showed little or no decrement. In contrast, for muscles of mdx mice and very old rats, forces transmitted laterally were impaired severely. Muscles of both mdx mice and very old rats showed major reductions in the expression of dystrophin. We conclude that during contractions, forces developed by skeletal muscles of young WT mice and rats are transmitted laterally from fibre to fibre through the DGC without decrement. In contrast, in muscles of dystrophic or very old animals, disruptions in DGC structure and function impair lateral transmission of force causing instability and increased susceptibility of fibres to contraction-induced injury.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2200, USA.
authors.forename: Krishnan S
authors.initials: KS
authors.lastname: Ramaswamy
authors.forename: Mark L
authors.initials: ML
authors.lastname: Palmer
authors.forename: Jack H
authors.initials: JH
authors.lastname: van der Meulen
authors.forename: Abigail
authors.initials: A
authors.lastname: Renoux
authors.forename: Tatiana Y
authors.initials: TY
authors.lastname: Kostrominova
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Michele
authors.forename: John A
authors.initials: JA
authors.lastname: Faulkner
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats
chemical_list: D016189:Dystrophin