Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is maintained but is not mechanistic in muscle sparing

Abstract

Extraocular muscle is uniquely spared from damage in merosin-deficient congenital muscular dystrophy. Using a murine model, we have tested the hypothesis that the maintenance of calcium homeostasis is mechanistic in extraocular muscle protection. Atomic absorption spectroscopy has demonstrated a strong correlation between the perturbation of calcium homeostasis in hindlimb muscle that is severely damaged and the absence of changes in calcium in extraocular muscle. If, as in other skeletal muscles, extraocular muscle fibers are destabilized by merosin deficiency, we would expect an increase in total muscle calcium coupled with an adaptive response in the high capacity/speed of the sarcoplasmic reticulum of the eye muscle. However, we have not observed the expected increases in total muscle calcium content, Ca²⁺-ATPase activity, Na⁺/Ca²⁺ exchanger content, or smooth ER Ca²⁺-ATPase content that are predicted by this model. Instead, these results indicate that the increased membrane permeability that characterizes, and is potentially mechanistic in, myofiber degeneration in muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus, the high-capacity calcium-scavenging systems are not primarily responsible for extraocular muscle protection in muscular dystrophy.