Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats

Abstract

Non-technical summaryThe force developed by a single fibre in frog muscles is transmitted laterally to the muscle surface with little or no loss. To demonstrate this phenomenon in mammals, a 'yoke' apparatus was developed that attached to the surface of whole, parallel-fibred muscles and permitted measurements of the lateral transmission of forces. We then demonstrated that for wild-type mice and rats longitudinal and lateral transmission of forces in muscles were not different. In contrast, for skeletal muscles of dystrophic mice and very old rats, in which the dystrophin-associated glycoprotein complex (DGC) of fibres was disrupted, the forces transmitted laterally were impaired severely. We conclude that during contractions of skeletal muscles, an intact DGC is essential for the lateral transmission of force and disruptions of the DGC lead to sarcomere instability and contraction-induced injury.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. Abbreviations ATB, anterior tibialis; DGC, dystrophin-associated glycoprotein complex; ECM, extracellular matrix; EDL, extensor digitorum longus.

New insights on contraction efficiency in patients with Duchenne muscular dystrophy

“…This assumption has been corroborated by ex vivo studies showing that both lateral (29) and longitudinal (6) force transmission are altered in mdx mice. To our knowledge, this alteration in force transmission has not been quantified in vivo.…”

“…These results confirm that the absence of dystrophin in DMD patients may lead to an increase in the time to transmit the force from actin filaments to the tendon (i.e., impairment of the longitudinal and lateral force transmission pathways; Refs. 6,29). This result may be partly explained by muscle structural abnormalities at two levels.…”

Evaluation and Imaging of an Untreated Grade III Hamstring Tear: A Case Report

“…Proximally, the semitendinosus and biceps are at the highest risk for injury owing to the pennation angle of their myofibers attaching to the common tendon of the hamstring complex [2]. The force generated by muscle is transmitted not only longitudinally along the axis of the muscle, but also radially to nearby muscles [17,34,38]. This altered pathway to transmit force to and along nearby muscles could minimize any functional deficits that would be detected if an injured muscle were tested in isolation instead of as part of a functional complex [4,17,32,41].…”

Adaptive strength gains in dystrophic muscle exposed to repeated bouts of eccentric contraction

“…Normally, dystrophin acts in combination with other cytoskeletal proteins in the costameric lattice to connect the sarcomere to the extracellular matrix (11,12). In this capacity, dystrophin helps facilitate the lateral transmission of contractile force and maintains sarcolemmal integrity (5,33,35) and intracellular Ca 2ϩ homeostasis (1,14). The general assumption is that the loss of dystrophin weakens the costameric lattice and renders fibers susceptible to eccentric contraction-induced injury.…”