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

A lack of dystrophin results in muscle degeneration in Duchenne muscul ar dystrophy. Dystrophin-deficient human and mouse muscle cells have h igher resting levels of intracellular free calcium ([Ca2+](i)) and sho w a related increase in single-channel open probabilities of calcium l eak channels. Elevated [Ca2+](i) results in high levels of calcium-dep endent proteolysis, which in turn increases calcium leak channel activ ity. This process could initiate muscle degeneration by further increa sing [Ca2+](i) and proteolysis in a-positive feedback loop. Here, we t ested 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 sh own to have normal dystrophin localization and no muscle degeneration. Fura-2 calcium measurements and single-channel patch recordings showe d 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 dyst rophin. Thus, restoration of normal calcium regulation in transgenic m dx mice may underlie the resulting absence of degeneration.