Isotonic fatigue in laminin alpha2-deficient dy/dy dystrophic mouse diaphragm.
Laminin alpha2 deficiency causes approximately 50% of human congenital muscular dystrophies. Muscle in the corresponding dy/dy mouse model has reduced force but increased fatigue resistance during isometric contractions. To determine whether a similar pattern of alterations is present during isotonic contractions, dy/dy diaphragm was studied in vitro. During 20% load, dystrophic diaphragm had significantly reduced shortening, shortening velocity, work and power deficits, which persisted during the fatigue-inducing stimulation. In contrast, during 40% load, isotonic contractile performance of diseased muscle was impaired only mildly and only for some contractile parameters. At both loads, rate of isotonic fatigue when expressed relative to initial contractile values was similar for dystrophic and normal muscle, or in some instances slightly higher for dystrophic muscle. Therefore, fatigue resistance is considerably impaired during isotonic contractions relative to that reported previously for isometric contractions. This has important implications for increased susceptibility to respiratory failure in laminin alpha2-deficient muscular dystrophy.
Department of Medicine, Case Western Reserve University, 10701 East Boulevard, Cleveland, Ohio 44106, USA. jmp56@cwru.edu
Jennifer
J
Pollarine
Michelle
M
Moyer
Erik
E
Van Lunteren
D000704:Analysis of Variance; D000818:Animals; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D007551:Isotonic Contraction / Q000235:genetics*; D007797:Laminin / Q000172:deficiency*; D008297:Male; D051379:Mice; D018763:Muscle Fatigue / Q000235:genetics*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D007797:Laminin; C102645:laminin alpha 2