MYOTUBES FROM TRANSGENIC MDX MICE EXPRESSING FULL-LENGTH DYSTROPHIN SHOW NORMAL CALCIUM REGULATION

A lack of dystrophin results in muscle degeneration in Duchenne muscular dystrophy. Dystrophin-deficient human and mouse muscle cells have higher resting levels of intracellular free calcium ([Ca2+](i)) and show a related increase in single-channel open probabilities of calcium leak channels. Elevated [Ca2+](i) results in high levels of calcium-dependent proteolysis, which in turn increases calcium leak channel activity. This process could initiate muscle degeneration by further increasing [Ca2+](i) and proteolysis in a-positive feedback loop. Here, we tested the direct effect of restoration of dystrophin on [Ca2+](i) and channel activity in primary myotubes from mdx mice made transgenic for full-length dystrophin. : Transgenic mdx mice have been previously shown to have normal dystrophin localization and no muscle degeneration. Fura-2 calcium measurements and single-channel patch recordings showed that resting [Ca2+](i) levels and open probabilities of calcium leak channels of transgenic mdx myotubes were similar to normal levels and significantly lower than mdx littermate controls (mdx) that lack dystrophin. Thus, restoration of normal calcium regulation in transgenic mdx mice may underlie the resulting absence of degeneration.