The sarcoplasmic reticulum calcium pump is functionally altered in dystrophic muscle

In Duchenne muscular dystrophy, muscle cells, which lack the protein dystrophin, have been reported to have elevated resting intracellular calcium 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 regulation of Ca2+ influx. A secondary alteration in the sarcoplasmic reticulum Ca2+ pump, however, could also contribute to, or be responsible for, the abnormal Ca2+ handling seen. To determine whether the Ca2+ pump is functionally altered in dystrophic muscle, we examined Ca2+ uptake by vesicles derived from skeletal muscle sarcoplasmic reticulum of normal and dystrophic (mdx) mice. The Hill coefficient and the Ca2+ sensitivity 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.