THE SARCOPLASMIC-RETICULUM CALCIUM-PUMP IS FUNCTIONALLY ALTERED IN DYSTROPHIC MUSCLE

In Duchenne muscular dystrophy, muscle cells, which lack the protein d ystrophin, have been reported to have elevated resting intracellular c alcium levels. It has also been noted that, compared to normal muscle, intracellular [Ca2+] in dystrophic muscle returns more slowly to its resting level following contractile stimulation. Consistent with this, it has been suggested that dystrophin is directly involved in the reg ulation of Ca2+ influx. A secondary alteration in the sarcoplasmic ret iculum Ca2+ pump, however, could also contribute to, or be responsible for, the abnormal Ca2+ handling seen. To determine whether the Ca2+ p ump is functionally altered in dystrophic muscle, we examined Ca2+ upt ake by vesicles derived from skeletal muscle sarcoplasmic reticulum of normal and dystrophic (mdx) mice. The Hill coefficient and the Ca2+ s ensitivity of the Ca2+ ATPase were the same in both cases, The maximum velocity of Ca2+ uptake, however, normalized to the ATPase content of the vesicles, was less for mdx muscle.