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.

Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle

“…The absence of the M-line system is consistent with known cytoskeletal organization differences between extraocular and other skeletal musculature (Cheng and Porter, 2002;Porter et al, 2001a) and suggests that eye muscle may use novel mechanisms to transmit contractile force to the sarcolemma and tendon. We speculate that such differences in the myofilament-cytoskeleton-sarcolemma-extracellular matrix linkage may underlie the established protection of EOM in dystrophin-glycoprotein complex-based muscular dystrophies (Kaminski et al, 1992;Karpati and Carpenter, 1986;Khurana et al, 1995;Porter and Karathanasis, 1998;Porter et al, , 2001bRagusa et al, 1996).…”

Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency

“…EOMs remain anatomically and functionally spared even at the late stages of the disease despite the severe pathology observed in other skeletal muscles (Kaminski et al, 1992; Khurana et al, 1995). Likewise, EOMs are spared in animal models of muscular dystrophy resulting from the absence of dystrophin or other dystroglycan complex-related proteins (Khurana et al, 1995; Porter and Karathanasis, 1998; Porter et al, 2001). The mechanism behind EOM sparing has remained unclear (Pacheco-Pinedo et al, 2009; Porter, 1998; Zeiger et al, 2010), but specific properties of EOM myogenic progenitors have been proposed as possible contributory factors (Kallestad et al, 2011; Porter et al, 2006).…”

Extraocular muscle is spared upon complete laminin α2 chain deficiency: Comparative expression of laminin and integrin isoforms

“…Interestingly, extraocular muscle (EOM) is uniquely spared from dystrophic damage in a mouse model for partial LMα2 chain deficiency (the dy/dy mouse) (Porter and Karathanasis, 1998). In other types of muscular dystrophy EOM is also spared (Porter, 2002).…”