Increased protein degradation results from elevated free calcium levels found in muscle from mdx mice

The defective gene responsible for Duchenne muscular dystrophy in humans and the dystrophic condition in mdx mice results in a lack of dystrophin at first thought to be localized to the triads, but more recently found on the cytoplasmic side of the sarcolemma of skeletal muscle fibres. Because the total calcium content of dystrophic fibres is significantly raised, we have compared the intracellular free calcium concentration [( Ca2+]i) in skeletal muscle in normal and mdx mice. We find that [Ca2+]i is markedly elevated in mdx muscle fibres compared with normal fibres, both at rest and during stimulation. By measuring protein degradation rates and manipulating [Ca2+]i, we have been able to demonstrate directly that the elevation of [Ca2+]i in mdx fibres results in an enhanced net degradation of muscle proteins.