EXTRAOCULAR-MUSCLE IN MEROSIN-DEFICIENT MUSCULAR-DYSTROPHY - CATION HOMEOSTASIS IS MAINTAINED BUT IS NOT MECHANISTIC IN MUSCLE SPARING

Extraocular muscle is uniquely spared from damage in merosin-deficient congenital muscular dystrophy. Using a murine model, we have tested t he hypothesis that the maintenance of calcium homeostasis is mechanist ic in extraocular muscle protection. Atomic absorption spectroscopy ha s demonstrated a strong correlation between the perturbation of calciu m homeostasis in hindlimb muscle that is severely damaged and the abse nce of changes in calcium in extraocular muscle. If, as in other skele tal muscles, extraocular muscle fibers are destabilized by merosin def iciency, we would expect an increase in total muscle calcium coupled w ith an adaptive response in the high capacity/speed of the sarcoplasmi c reticulum of the eye muscle. However, we have not observed the expec ted increases in total muscle calcium content, Ca2+-ATPase activity, N a+/Ca2+ exchanger content, or smooth ER Ca2+-ATPase content that are p redicted by this model. Instead, these results indicate that the incre ased membrane permeability that characterizes, and is potentially mech anistic in, myofiber degeneration in muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus, the high-capacity calc ium-scavenging systems are not primarily responsible for extraocular m uscle protection in muscular dystrophy.