Dystrophin protects the sarcolemma from stresses developed during muscle contraction.
The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse.
Petrof
B J
BJ
Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia 19104.
Shrager
J B
JB
Stedman
H H
HH
Kelly
A M
AM
Sweeney
H L
HL
D000818:Animals; D016189:Dystrophin / Q000235:genetics / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000502:physiology* / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology*; D012508:Sarcolemma / Q000502:physiology* / Q000648:ultrastructure*; D013314:Stress, Mechanical
D016189:Dystrophin