Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stress.
Loss of the dystrophin-glycoprotein complex from muscle sarcolemma in Duchenne's muscular dystrophy (DMD) renders the membrane susceptible to mechanical injury, leaky to Ca(2+), and disrupts signaling, but the precise mechanism(s) leading to the onset of DMD remain unclear. To assess the role of mechanical injury in the onset of DMD, extensor digitorum longus (EDL) muscles from C57 (control), mdx, and mdx-utrophin-deficient [mdx:utrn(-/-); dystrophic] pups aged 9-12 days were subjected to an acute stretch-injury or no-stretch protocol in vitro. Before the stretches, isometric stress was attenuated for mdx:utrn(-/-) compared with control muscles at all stimulation frequencies (P < 0.05). During the stretches, EDL muscles for each genotype demonstrated similar mean stiffness values. After the stretches, isometric stress during a tetanus was decreased significantly for both mdx and mdx:utrn(-/-) muscles compared with control muscles (P < 0.05). Membrane injury assessed by uptake of procion orange dye was greater for dystrophic compared with control EDL (P < 0.05), but, within each genotype, the percentage of total cells taking up dye was not different for the no-stretch vs. stretch condition. These data suggest that the sarcolemma of maturing dystrophic EDL muscles are resistant to acute mechanical injury.
Grange
Robert W
RW
Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0430, USA. rgrange@vt.edu
Gainer
Thomas G
TG
Marschner
Krista M
KM
Talmadge
Robert J
RJ
Stull
James T
JT
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005838:Genotype; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D012016:Reference Values; D013314:Stress, Mechanical; D049411:Utrophin
D003598:Cytoskeletal Proteins; D005456:Fluorescent Dyes; D008565:Membrane Proteins; C483600:Utrn protein, mouse; D049411:Utrophin