EXCITATION-CONTRACTION COUPLING IS DISRUPTED IN FAST MUSCLE FIBERS FROM DYSTROPHIC MDX MICE

Abstract

The mdx mouse is a widely used animal model for Duchenne muscular dystrophy. Little is known about the functional characteristics of excitation-contraction (E-C) coupling in muscle fibers of mdx mice. PURPOSE To determine whether E-C coupling and sarcoplasmic reticulum (SR) function in mechanically skinned single muscle fibers from mdx mice is abnormal. METHODS Fibers were prepared from fast twitch extensor digitorum longus (EDL) muscles of adult control (C57BL/10 ScSn) and dystrophic (mdx) mice that where killed by rapid cervical dislocation. Depolarization-induced contraction (DICR) and SR function of individual fibers was determined by Na+/K+ substitution in Ca2+-buffered solutions. RESULTS Peak DICR was similar in fibers from mdx and control mice, however, run down (DICR <50% of initial) was reached more rapidly in fibers from mdx mice [control, 32 ± 5 depolarizations (n = 14 fibers) vs. mdx, 18 ± 1 depolarizations (n = 7 fibers), P <0.05]. Normalized SR Ca2+ reloading and leak was not different but SR Ca2+ release measured from caffeine contraction (2–7 mM) was decreased in mdx compared to control mice (P <0.05). CONCLUSIONS Voltage activated contraction is normal in mdx muscle fibers but repeated activation is disrupted indicating subtle changes in E-C coupling. Supported by the Muscular Dystrophy Association (USA)