ABSENCE OF EXTRAOCULAR-MUSCLE PATHOLOGY IN DUCHENNES MUSCULAR-DYSTROPHY - ROLE FOR CALCIUM HOMEOSTASIS IN EXTRAOCULAR-MUSCLE SPARING

Duchenne muscular dystrophy (DMD) is characterized by clinical weaknes s and progressive necrosis of striated muscle as a consequence of dyst rophin deficiency. While all skeletal muscle groups are thought to be affected, enigmatically, the extraocular muscles (EOM) appear clinical ly unaffected. Here we show that dystrophin deficiency does not result in myonecrosis or pathologically elevated levels of intracellular cal cium ([Ca2+](i)) in EOM. At variance with a previous report, we find n o evidence for dystrophin-related protein/utrophin up-regulation in EO M. In vitro experiments demonstrate that extraocular muscles are inher ently more resistant to necrosis caused by pharmacologically elevated [Ca2+](i) levels when compared with pectoral musculature. We believe t hat EOM are spared in DMD because of their intrinsic ability to mainta in calcium homeostasis better than other striated muscle groups. Our r esults indicate that modulating levels of [Ca2+](i) in muscle may be o f potential therapeutic use in DMD.